Sabervel
ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Sabervel 75 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 75 mg of irbesartan 
 
Excipient with known effect:  
20 mg of lactose monohydrate per film-coated tablet 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet. 
White, concave, round, film-coated tablet with 7 mm diameter.  
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications  
 
Sabervel is indicated in adults for the treatment of essential hypertension. 
It is also indicated for the treatment of renal disease in adult patients with hypertension and type 2 
diabetes mellitus as part of an antihypertensive medicinal product regimen (see sections 4.3, 4.4, 4.5 
and 5.1). 
 
4.2 Posology and method of administration 
 
Posology 
 
The usual recommended initial and maintenance dose is 150 mg once daily, with or without food. 
Sabervel at a dose of 150 mg once daily generally provides a better 24 hour blood pressure control 
than 75 mg. However, initiation of therapy with 75 mg could be considered, particularly in 
haemodialysed patients and in the elderly over 75 years. 
 
In patients insufficiently controlled with 150 mg once daily, the dose of Sabervel can be increased to 
300 mg, or other antihypertensive agents can be added (see sections 4.3, 4.4, 4.5 and 5.1). In 
particular, the addition of a diuretic such as hydrochlorothiazide has been shown to have an additive 
effect with Sabervel (see section 4.5). 
 
In hypertensive type 2 diabetic patients, therapy should be initiated at 150 mg irbesartan once daily 
and titrated up to 300 mg once daily as the preferred maintenance dose for treatment of renal disease. 
The demonstration of renal benefit of Sabervel in hypertensive type 2 diabetic patients is based on 
studies where irbesartan was used in addition to other antihypertensive agents, as needed, to reach 
target blood pressure (see sections 4.3, 4.4, 4.5 and 5.1). 
 
Special Populations 
 
Renal impairment: no dosage adjustment is necessary in patients with impaired renal function. A 
lower starting dose (75 mg) should be considered for patients undergoing haemodialysis (see section 
4.4). 
 
Hepatic impairment: no dosage adjustment is necessary in patients with mild to moderate hepatic 

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impairment. There is no clinical experience in patients with severe hepatic impairment. 
 
Elderly patients: although consideration should be given to initiating therapy with 75 mg in patients 
over 75 years of age, dosage adjustment is not usually necessary for the elderly. 
 
Paediatric population: the safety and efficacy of Sabervel in children aged 0 to 18 has not been 
established. Currently available data are described in section 4.8, 5.1 and 5.2 but no recommendation 
on a posology can be made. 
 
Method of Administration 
 
For oral use. 
 
4.3 Contraindications  
 
Hypersensitivity to the active substance, or to any of the excipients (see section 6.1).  
Second and third trimesters of pregnancy (see sections 4.4 and 4.6). 
 
The concomitant use of Sabervel with aliskiren-containing products is contraindicated in patients with 
diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m2) (see sections 4.5 and 5.1). 
 
4.4 Special warnings and precautions for use  
 
Intravascular volume depletion: symptomatic hypotension, especially after the first dose, may occur in 
patients who are volume and/or sodium depleted by vigorous diuretic therapy, dietary salt restriction, 
diarrhoea or vomiting. Such conditions should be corrected before the administration of Sabervel. 
 
Renovascular hypertension: there is an increased risk of severe hypotension and renal insufficiency 
when patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney 
are treated with medicinal products that affect the renin-angiotensin-aldosterone system. While this is 
not documented with Sabervel, a similar effect should be anticipated with angiotensin-II receptor 
antagonists. 
 
Renal impairment and kidney transplantation: when Sabervel is used in patients with impaired renal 
function, a periodic monitoring of potassium and creatinine serum levels is recommended. There is no 
experience regarding the administration of Sabervel in patients with a recent kidney transplantation. 
 
Hypertensive patients with type 2 diabetes and renal disease: the effects of irbesartan both on renal and 
cardiovascular events were not uniform across all subgroups, in an analysis carried out in the study 
with patients with advanced renal disease. In particular, they appeared less favourable in women and 
non-white subjects (see section 5.1). 
 
Dual blockade of the renin-angiotensin-aldosterone system (RAAS) 
There is evidence that the concomitant use of ACE-inhibitors, angiotensin II receptor blockers or 
aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including 
acute renal failure). Dual blockade of RAAS through the combined use of ACE-inhibitors, angiotensin 
II receptor blockers or aliskiren is therefore not recommended (see sections 4.5 and 5.1). 
If dual blockade therapy is considered absolutely necessary, this should only occur under specialist 
supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure. 
ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with 
diabetic nephropathy. 
 
Hyperkalaemia: as with other medicinal products that affect the renin-angiotensin-aldosterone system, 
hyperkalaemia may occur during the treatment with Sabervel, especially in the presence of renal 
impairment, overt proteinuria due to diabetic renal disease, and/or heart failure. Close monitoring of 
serum potassium in patients at risk is recommended (see section 4.5). 
 

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Lithium: the combination of lithium and Sabervel is not recommended (see section 4.5). 
 
Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy: as with other vasodilators, 
special caution is indicated in patients suffering from aortic or mitral stenosis, or obstructive 
hypertrophic cardiomyopathy. 
 
Primary aldosteronism: patients with primary aldosteronism generally will not respond to 
antihypertensive medicinal products acting through inhibition of the renin-angiotensin system. 
Therefore, the use of Sabervel is not recommended. 
 
General: in patients whose vascular tone and renal function depend predominantly on the activity of 
the renin-angiotensin-aldosterone system (e.g. patients with severe congestive heart failure or 
underlying renal disease, including renal artery stenosis), treatment with angiotensin converting 
enzyme inhibitors or angiotensin-II receptor antagonists that affect this system has been associated 
with acute hypotension, azotaemia, oliguria, or rarely acute renal failure. As with any antihypertensive 
agent, excessive blood pressure decrease in patients with ischaemic cardiopathy or ischaemic 
cardiovascular disease could result in a myocardial infarction or stroke. 
As observed for angiotensin converting enzyme inhibitors, irbesartan and the other angiotensin 
antagonists are apparently less effective in lowering blood pressure in black people than in non-blacks, 
possibly because of higher prevalence of low-renin states in the black hypertensive population (see 
section 5.1). 
 
Pregnancy: Angiotensin II Receptor Antagonists (AIIRAs) should not be initiated during pregnancy.  
Unless continued AIIRA therapy is considered essential, patients planning pregnancy should be 
changed to alternative antihypertensive treatments which have an established safety profile for use in 
pregnancy. When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, 
and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.6). 
 
Lactose: this medicinal product contains lactose. Patients with rare hereditary problems of galactose 
intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this 
medicinal product. 
 
Paediatric population: irbesartan has been studied in paediatric populations aged 6 to 16 years old but 
the current data are insufficient to support an extension of the use in children until further data become 
available (see sections 4.8, 5.1 and 5.2). 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Diuretics and other antihypertensive agents: other antihypertensive agents may increase the 
hypotensive effects of irbesartan; however  irbesartan has been safely administered with other 
antihypertensive agents, such as beta-blockers, long-acting calcium channel blockers, and thiazide 
diuretics. Prior treatment with high dose diuretics may result in volume depletion and a risk of 
hypotension when initiating therapy with Sabervel (see section 4.4). 
 
Clinical trial data has shown that dual blockade of the renin-angiotensin-aldosterone-system (RAAS) 
through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is associated 
with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal 
function (including acute renal failure) compared to the use of a single RAAS-acting agent (see 
sections 4.3, 4.4 and 5.1). 
 
Potassium supplements and potassium-sparing diuretics: based on experience with the use of other 
medicinal products that affect the renin-angiotensin system, concomitant use of potassium-sparing 
diuretics, potassium supplements, salt substitutes containing potassium or other medicinal products 
that may increase serum potassium levels (e.g. heparin) may lead to increases in serum potassium and 
is, therefore, not recommended (see section 4.4). 
 
Lithium: reversible increases in serum lithium concentrations and toxicity have been reported during 

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concomitant administration of lithium with angiotensin converting enzyme inhibitors. Similar effects 
have been very rarely reported with irbesartan so far. Therefore, this combination is not recommended 
(see section 4.4). If the combination proves necessary, careful monitoring of serum lithium levels is 
recommended. 
 
Non-steroidal anti-inflammatory drugs: when angiotensin II antagonists are administered 
simultaneously with non-steroidal anti-inflammatory drugs (i.e. selective COX-2 inhibitors, 
acetylsalicylic acid (> 3 g/day) and non-selective NSAIDs), attenuation of the antihypertensive effect 
may occur. 
As with ACE inhibitors, concomitant use of angiotensin II antagonists and NSAIDs may lead to an 
increased risk of worsening of renal function, including possible acute renal failure, and an increase in 
serum potassium, especially in patients with poor pre-existing renal function. The combination should 
be administered with caution, especially in the elderly. Patients should be adequately hydrated and 
consideration should be given to monitoring renal function after initiation of concomitant therapy, and 
periodically thereafter. 
 
Additional information on irbesartan interactions: in clinical studies, the pharmacokinetic of irbesartan 
is not affected by hydrochlorothiazide. Irbesartan is mainly metabolised by CYP2C9 and to a lesser 
extent by glucuronidation. No significant pharmacokinetic or pharmacodynamic interactions were 
observed when irbesartan was coadministered with warfarin, a medicinal product metabolised by 
CYP2C9. The effects of CYP2C9 inducers such as rifampicin on the pharmacokinetic of irbesartan 
have not been evaluated. The pharmacokinetic of digoxin was not altered by coadministration of 
irbesartan. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy: 
 
The use of AIIRAs is not recommended during the first trimester of pregnancy (see section 4.4). The 
use of AIIRAs is contraindicated during the second and third trimesters of pregnancy (see sections 4.3 
and 4.4). 
 
Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors 
during the first trimester of pregnancy has not been conclusive; however a small increase in risk 
cannot be excluded. Whilst there is no controlled epidemiological data on the risk with Angiotensin II 
Receptor Antagonists (AIIRAs), similar risks may exist for this class of drugs. Unless continued 
AIIRA therapy is considered essential, patients planning pregnancy should be changed to alternative 
antihypertensive treatments which have an established safety profile for use in pregnancy. When 
pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, and, if appropriate, 
alternative therapy should be started. 
 
Exposure to AIIRA therapy during the second and third trimesters is known to induce human 
fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal 
toxicity (renal failure, hypotension, hyperkalaemia). (See section 5.3). 
Should exposure to AIIRAs have occurred from the second trimester of pregnancy, ultrasound check 
of renal function and skull is recommended. 
Infants whose mothers have taken AIIRAs should be closely observed for hypotension (see sections 
4.3 and 4.4). 
 
Breast-feeding: 
 
Because no information is available regarding the use of Sabervel during breast-feeding, Sabervel is 
not recommended and alternative treatments with better established safety profiles during breast-
feeding are preferable, especially while nursing a newborn or preterm infant. 
 
It is unknown whether irbesartan or its metabolites are excreted in human milk. 
Available pharmacodynamic/toxicological data in rats have shown excretion of irbesartan or its 

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metabolites in milk (for details see 5.3). 
 
Fertility 
 
Irbesartan had no effect upon fertility of treated rats and their offspring up to the dose levels inducing 
the first signs of parental toxicity (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
No studies on the effects on the ability to drive and use machines have been performed. Based on its 
pharmacodynamic properties, irbesartan is unlikely to affect this ability. When driving vehicles or 
operating machines, it should be taken into account that dizziness or weariness may occur during 
treatment. 
 
4.8 Undesirable effects 
 
In placebo-controlled trials in patients with hypertension, the overall incidence of adverse events did 
not differ between the irbesartan (56.2%) and the placebo groups (56.5%). Discontinuation due to any 
clinical or laboratory adverse event was less frequent for irbesartan-treated patients (3.3%) than for 
placebo-treated patients (4.5%). The incidence of adverse events was not related to dose (in the 
recommended dose range), gender, age, race, or duration of treatment. 
 
In diabetic hypertensive patients with microalbuminuria and normal renal function, orthostatic 
dizziness and orthostatic hypotension were reported in 0.5% of the patients (i.e., uncommon) but in 
excess of placebo. 
 
The following table presents the adverse drug reactions that were reported in placebo-controlled trials 
in which 1,965 hypertensive patients received irbesartan. Terms marked with a star (*) refer to the 
adverse reactions that were additionally reported in > 2% of diabetic hypertensive patients with 
chronic renal insufficiency and overt proteinuria and in excess of placebo. 
 
The frequency of adverse reactions listed below is defined using the following convention: 
very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare 
(≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000). Within each frequency grouping, undesirable effects 
are presented in order of decreasing seriousness. 
 
Adverse reactions additionally reported from post–marketing experience are also listed. These adverse 
reactions are derived from spontaneous reports. 
 
Immune system disorders: 
Not known:  hypersensitivity reactions such as angioedema, rash, urticaria 
 
Metabolism and nutrition disorders: 
Not known:  hyperkalaemia 
 
Nervous system disorders: 
Common:  dizziness, orthostatic dizziness* 
Not known:  vertigo, headache 
 
Ear and labyrinth disorder: 
Not known:  tinnitus 
 
Cardiac disorders: 
Uncommon:  tachycardia 
 
Vascular disorders: 
Common:  orthostatic hypotension* 

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Uncommon:  flushing 
 
Respiratory, thoracic and mediastinal disorders: 
Uncommon:  cough 
 
Gastrointestinal disorders: 
Common:  nausea/vomiting 
Uncommon:  diarrhoea, dyspepsia/heartburn 
Not known:   dysgeusia 
 
Hepatobiliary disorders: 
Uncommon:  jaundice 
Not known:   hepatitis, abnormal liver function 
 
Skin and subcutaneous tissue disorders: 
Not known:   leukocytoclastic vasculitis 
 
Musculoskeletal and connective tissue disorders: 
Common:  musculoskeletal pain* 
Not known: arthralgia, myalgia (in some cases associated with increased plasma creatine kinase 

levels), muscle cramps 
 
Renal and urinary disorders: 
Not known:  impaired renal function including cases of renal failure in patients at risk (see 
section 4.4) 
 
Reproductive system and breast disorders: 
Uncommon:  sexual dysfunction 
 
General disorders and administration site conditions: 
Common:  fatigue 
Uncommon:  chest pain 
 
Investigations: 
Very common: Hyperkalaemia* occurred more often in diabetic patients treated with 

irbesartan than with placebo. In diabetic hypertensive patients with 
microalbuminuria and normal renal function, hyperkalaemia (≥ 
5.5 mEq/L) occurred in 29.4% of the patients in the irbesartan 300 mg 
group and 22% of the patients in the placebo group. In diabetic 
hypertensive patients with chronic renal insufficiency and overt 
proteinuria, hyperkalaemia (≥ 5.5 mEq/L) occurred in 46.3% of the 
patients in the irbesartan group and 26.3% of the patients in the placebo 
group. 

Common: significant increases in plasma creatine kinase were commonly observed 
(1.7%) in irbesartan treated subjects. None of these increases were 
associated with identifiable clinical musculoskeletal events. 
In 1.7% of hypertensive patients with advanced diabetic renal disease 
treated with irbesartan, a decrease in haemoglobin*, which was not 
clinically significant, has been observed. 

 
Paediatric population:  
In a randomised trial of 318 hypertensive children and adolescents aged 6 to 16 years, the following 
adverse reactions occurred in the 3-week double-blind phase: headache (7.9%), hypotension (2.2%), 
dizziness (1.9%), cough (0.9%). In the 26-week open-label period of this trial the most frequent 
laboratory abnormalities observed were creatinine increases (6.5%) and elevated CK values in 2% of 
child recipients. 
 

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4.9 Overdose 
 
Experience in adults exposed to doses of up to 900 mg/day for 8 weeks revealed no toxicity. The most 
likely manifestations of overdose are expected to be hypotension and tachycardia; bradycardia might 
also occur from overdose. No specific information is available on the treatment of overdose with 
Sabervel. The patient should be closely monitored, and the treatment should be symptomatic and 
supportive. Suggested measures include induction of emesis and/or gastric lavage. Activated charcoal 
may be useful in the treatment of overdose. Irbesartan is not removed by haemodialysis. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Angiotensin-II antagonists, plain.  
ATC code: C09C A04. 
 
Mechanism of action: Irbesartan is a potent, orally active, selective angiotensin-II receptor (type AT1) 
antagonist. It is expected to block all actions of angiotensin-II mediated by the AT1 receptor, 
regardless of the source or route of synthesis of angiotensin-II. The selective antagonism of the 
angiotensin-II (AT1) receptors results in increases in plasma renin levels and angiotensin-II levels, and 
a decrease in plasma aldosterone concentration. Serum potassium levels are not significantly affected 
by irbesartan alone at the recommended doses. Irbesartan does not inhibit ACE (kininase-II), an 
enzyme which generates angiotensin-II and also degrades bradykinin into inactive metabolites. 
 
Irbesartan does not require metabolic activation for its activity.  
 
Clinical efficacy: 
Hypertension 
Irbesartan lowers blood pressure with minimal change in heart rate. The decrease in blood pressure is 
dose-related for once a day doses with a tendency towards plateau at doses above 300 mg. Doses of 
150-300 mg once daily lower supine or seated blood pressures at trough (i.e. 24 hours after dosing) by 
an average of 8-13/5-8 mm Hg (systolic/diastolic) greater than those associated with placebo. 
Peak reduction of blood pressure is achieved within 3-6 hours after administration and the blood 
pressure lowering effect is maintained for at least 24 hours. At 24 hours the reduction of blood 
pressure was 60-70% of the corresponding peak diastolic and systolic responses at the recommended 
doses. Once daily dosing with 150 mg produced trough and mean 24 hour responses similar to twice 
daily dosing on the same total dose. 
 
The blood pressure lowering effect of irbesartan is evident within 1-2 weeks, with the maximal effect 
occurring by 4-6 weeks after start of therapy. The antihypertensive effects are maintained during long 
term therapy. After withdrawal of therapy, blood pressure gradually returns toward baseline. Rebound 
hypertension has not been observed. 
The blood pressure lowering effects of irbesartan and thiazide-type diuretics are additive. In patients 
not adequately controlled by irbesartan alone, the addition of a low dose of hydrochlorothiazide 
(12.5 mg) to irbesartan once daily results in a further placebo-adjusted blood pressure reduction at 
trough of 7-10/3-6 mm Hg (systolic/diastolic). 
The efficacy of irbesartan is not influenced by age or gender. As is the case with other medicinal 
products that affect the renin-angiotensin system, black hypertensive patients have notably less 
response to irbesartan monotherapy. When irbesartan is administered concomitantly with a low dose of 
hydrochlorothiazide (e.g. 12.5 mg daily), the antihypertensive response in black patients approaches 
that of white patients. 
There is no clinically important effect on serum uric acid or urinary uric acid secretion. 
 
Paediatric population  
Reduction of blood pressure with 0.5 mg/kg (low), 1.5 mg/kg (medium) and 4.5 mg/kg (high) target 
titrated doses of irbesartan was evaluated in 318 hypertensive or at risk (diabetic, family history of 

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hypertension) children and adolescents aged 6 to 16 years over a three week period. At the end of the 
three weeks the mean reduction from baseline in the primary efficacy variable, trough seated systolic 
blood pressure (SeSBP) was 11.7 mmHg (low dose), 9.3 mmHg (medium dose), 13.2 mmHg (high 
dose). No significant difference was apparent between these doses. Adjusted mean change of trough 
seated diastolic blood pressure (SeDBP) was as follows: 3.8 mmHg (low dose), 3.2 mmHg (medium 
dose), 5.6 mmHg (high dose). Over a subsequent two week period where patients were re-randomized 
to either active medicinal product or placebo, patients on placebo had increases of 2.4 and 2.0 mmHg 
in SeSBP and SeDBP compared to +0.1 and -0.3 mmHg changes respectively in those on all doses of 
irbesartan (see section 4.2). 
 
Hypertension and type 2 diabetes with renal disease 
The “Irbesartan Diabetic Nephropathy Trial (IDNT)” shows that irbesartan decreases the progression 
of renal disease in patients with chronic renal insufficiency and overt proteinuria. IDNT was a double 
blind, controlled, morbidity and mortality trial comparing irbesartan, amlodipine and placebo. In 1,715 
hypertensive patients with type 2 diabetes, proteinuria ≥ 900 mg/day and serum creatinine ranging 
from 1.0-3.0 mg/dl, the long-term effects (mean 2.6 years) of irbesartan on the progression of renal 
disease and all-cause mortality were examined. Patients were titrated from 75 mg to a maintenance 
dose of 300 mg irbesartan, from 2.5 mg to 10 mg amlodipine, or placebo as tolerated.  
Patients in all treatment groups typically received between 2 and 4 antihypertensive agents (e.g., 
diuretics, beta blockers, alpha blockers) to reach a predefined blood pressure goal of ≤ 135/85 mmHg 
or a 10 mmHg reduction in systolic pressure if baseline was > 160 mmHg. Sixty per cent (60%) of 
patients in the placebo group reached this target blood pressure whereas this figure was 76% and 78% 
in the irbesartan and amlodipine groups respectively.  
Irbesartan significantly reduced the relative risk in the primary combined endpoint of doubling serum 
creatinine, end-stage renal disease (ESRD) or all-cause mortality. Approximately 33% of patients in 
the irbesartan group reached the primary renal composite endpoint compared to 39% and 41% in the 
placebo and amlodipine groups [20% relative risk reduction versus placebo (p = 0.024) and 23% 
relative risk reduction compared to amlodipine (p = 0.006)]. When the individual components of the 
primary endpoint were analysed, no effect in all cause mortality was observed, while a positive trend 
in the reduction in ESRD and a significant reduction in doubling of serum creatinine were observed. 
 
Subgroups consisting of gender, race, age, duration of diabetes, baseline blood pressure, serum 
creatinine, and albumin excretion rate were assessed for treatment effect. In the female and black 
subgroups which represented 32% and 26% of the overall study population respectively, a renal 
benefit was not evident, although the confidence intervals do not exclude it. As for the secondary 
endpoint of fatal and non-fatal cardiovascular events, there was no difference among the three groups 
in the overall population, although an increased incidence of non-fatal MI was seen for women and a 
decreased incidence of non-fatal MI was seen in males in the irbesartan group versus the placebo-
based regimen. An increased incidence of non-fatal MI and stroke was seen in females in the 
irbesartan-based regimen versus the amlodipine-based regimen, while hospitalization due to heart 
failure was reduced in the overall population. However, no proper explanation for these findings in 
women has been identified. 
 
The study of the “Effects of Irbesartan on Microalbuminuria in Hypertensive Patients with type 2 
Diabetes Mellitus (IRMA 2)” shows that irbesartan 300 mg delays progression to overt proteinuria in 
patients with microalbuminuria. IRMA 2 was a placebo-controlled double blind morbidity study in 
590 patients with type 2 diabetes, microalbuminuria (30-300 mg/day) and normal renal function 
(serum creatinine ≤ 1.5 mg/dl in males and < 1.1 mg/dl in females). The study examined the long-term 
effects (2 years) of irbesartan on the progression to clinical (overt) proteinuria (urinary albumin 
excretion rate (UAER) > 300 mg/day, and an increase in UAER of at least 30% from baseline). The 
predefined blood pressure goal was ≤ 135/85 mmHg. Additional antihypertensive agents (excluding 
ACE inhibitors, angiotensin II receptor antagonists and dihydropyridine calcium blockers) were added 
as needed to help achieve the blood pressure goal. While similar blood pressure was achieved in all 
treatment groups, fewer subjects in the irbesartan 300 mg group (5.2%) than in the placebo (14.9%) or 
in the irbesartan 150 mg group (9.7%) reached the endpoint of overt proteinuria, demonstrating a 70% 
relative risk reduction versus placebo (p = 0.0004) for the higher dose. An accompanying 
improvement in the glomerular filtration rate (GFR) was not observed during the first three months of 

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treatment. The slowing in the progression to clinical proteinuria was evident as early as three months 
and continued over the 2 year period. Regression to normoalbuminuria (< 30 mg/day) was more 
frequent in the irbesartan 300 mg group (34%) than in the placebo group (21%). 
 
Two large randomised, controlled trials (ONTARGET (ONgoing Telmisartan Alone and in 
combination with Ramipril Global Endpoint Trial) and VA NEPHRON-D (The Veterans Affairs 
Nephropathy in Diabetes)) have examined the use of the combination of an ACE-inhibitor with an 
angiotensin II receptor blocker. 
ONTARGET was a study conducted in patients with a history of cardiovascular or cerebrovascular 
disease, or type 2 diabetes mellitus accompanied by evidence of end-organ damage. VA NEPHRON-D 
was a study in patients with type 2 diabetes mellitus and diabetic nephropathy. 
These studies have shown no significant beneficial effect on renal and/or cardiovascular outcomes and 
mortality, while an increased risk of hyperkalaemia, acute kidney injury and/or hypotension as 
compared to monotherapy was observed. Given their similar pharmacodynamic properties, these 
results are also relevant for other ACE-inhibitors and angiotensin II receptor blockers. 
ACE-inhibitors and angiotensin II receptor blockers should therefore not be used concomitantly in 
patients with diabetic nephropathy. 
ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) 
was a study designed to test the benefit of adding aliskiren to a standard therapy of an ACE-inhibitor 
or an angiotensin II receptor blocker in patients with type 2 diabetes mellitus and chronic kidney 
disease, cardiovascular disease, or both. The study was terminated early because of an increased risk 
of adverse outcomes. Cardiovascular death and stroke were both numerically more frequent in the 
aliskiren group than in the placebo group and adverse events and serious adverse events of interest 
(hyperkalaemia, hypotension and renal dysfunction) were more frequently reported in the aliskiren 
group than in the placebo group. 
 
5.2 Pharmacokinetic properties 
 
After oral administration, irbesartan is well absorbed: studies of absolute bioavailability gave values of 
approximately 60-80%. Concomitant food intake does not significantly influence the bioavailability of 
irbesartan. Plasma protein binding is approximately 96%, with negligible binding to cellular blood 
components. The volume of distribution is 53 - 93 litres. Following oral or intravenous administration 
of 14C irbesartan, 80-85% of the circulating plasma radioactivity is attributable to unchanged 
irbesartan. Irbesartan is metabolised by the liver via glucuronide conjugation and oxidation. The major 
circulating metabolite is irbesartan glucuronide (approximately 6%). In vitro studies indicate that 
irbesartan is primarily oxidised by the cytochrome P450 enzyme CYP2C9; isoenzyme CYP3A4 has 
negligible effect. 
 
Irbesartan exhibits linear and dose proportional pharmacokinetics over the dose range of 10 to 600 mg. 
A less than proportional increase in oral absorption at doses beyond 600 mg (twice the maximal 
recommended dose) was observed; the mechanism for this is unknown. Peak plasma concentrations 
are attained at 1.5 - 2 hours after oral administration. The total body and renal clearance are 157 - 176 
and 3 - 3.5 ml/min, respectively. The terminal elimination half-life of irbesartan is 11 - 15 hours. 
Steady-state plasma concentrations are attained within 3 days after initiation of a once-daily dosing 
regimen. Limited accumulation of irbesartan (< 20%) is observed in plasma upon repeated once-daily 
dosing. In a study, somewhat higher plasma concentrations of irbesartan were observed in female 
hypertensive patients. However, there was no difference in the half-life and accumulation of 
irbesartan. No dosage adjustment is necessary in female patients. Irbesartan AUC and Cmax values 
were also somewhat greater in elderly subjects (≥ 65 years) than those of young subjects (18 - 40 
years). However the terminal half-life was not significantly altered. No dosage adjustment is necessary 
in elderly patients. 
 
Irbesartan and its metabolites are eliminated by both biliary and renal pathways. After either oral or IV 
administration of 14C irbesartan, about 20% of the radioactivity is recovered in the urine, and the 
remainder in the faeces. Less than 2% of the dose is excreted in the urine as unchanged irbesartan. 
 
Paediatric population 

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The pharmacokinetics of irbesartan were evaluated in 23 hypertensive children after the administration 
of single and multiple daily doses of irbesartan (2 mg/kg) up to a maximum daily dose of 150 mg for 
four weeks. Of those 23 children, 21 were evaluable for comparison of pharmacokinetics with adults 
(twelve children over 12 years, nine children between 6 and 12 years). Results showed that Cmax, 
AUC and clearance rates were comparable to those observed in adult patients receiving 150 mg 
irbesartan daily. A limited accumulation of irbesartan (18%) in plasma was observed upon repeated 
once daily dosing. 
 
Renal impairment: in patients with renal impairment or those undergoing haemodialysis, the 
pharmacokinetic parameters of irbesartan are not significantly altered. Irbesartan is not removed by 
haemodialysis. 
 
Hepatic impairment: in patients with mild to moderate cirrhosis, the pharmacokinetic parameters of 
irbesartan are not significantly altered. 
Studies have not been performed in patients with severe hepatic impairment. 
 
5.3 Preclinical safety data 
 
There was no evidence of abnormal systemic or target organ toxicity at clinically relevant doses. In 
non-clinical safety studies, high doses of irbesartan (≥ 250 mg/kg/day in rats and ≥ 100 mg/kg/day in 
macaques) caused a reduction of red blood cell parameters (erythrocytes, haemoglobin, haematocrit). 
At very high doses (≥ 500 mg/kg/day) degenerative changes in the kidney (such as interstitial 
nephritis, tubular distension, basophilic tubules, increased plasma concentrations of urea and 
creatinine) were induced by irbesartan in the rat and the macaque and are considered secondary to the 
hypotensive effects of the medicinal product which led to decreased renal perfusion. Furthermore, 
irbesartan induced hyperplasia/hypertrophy of the juxtaglomerular cells (in rats at ≥ 90 mg/kg/day, in 
macaques at ≥ 10 mg/kg/day). All of these changes were considered to be caused by the 
pharmacological action of irbesartan. For therapeutic doses of irbesartan in humans, the hyperplasia/ 
hypertrophy of the renal juxtaglomerular cells does not appear to have any relevance. 
 
There was no evidence of mutagenicity, clastogenicity or carcinogenicity. 
 
Fertility and reproductive performance were not affected in studies of male and female rats even at 
oral doses of irbesartan causing some parental toxicity (from 50 to 650 mg/kg/day), including 
mortality at the highest dose. No significant effects on the number of corpora lutea, implants, or live 
fetuses were observed. Irbesartan did not affect survival, development, or reproduction of offspring. 
Studies in animals indicate that the radiolabeled irbesartan is detected in rat and rabbit fetuses. 
Irbesartan is excreted in the milk of lactating rats. 
 
Animal studies with irbesartan showed transient toxic effects (increased renal pelvic cavitation, 
hydroureter or subcutaneous oedema) in rat foetuses, which were resolved after birth. In rabbits, 
abortion or early resorption were noted at doses causing significant maternal toxicity, including 
mortality. No teratogenic effects were observed in the rat or rabbit. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core: 
Lactose monohydrate  
Microcrystalline cellulose  
Croscarmellose sodium  
Silica colloidal anhydrous 
Hypromellose 
Magnesium stearate. 
 

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Film-coating: 
Hypromellose  
Titanium dioxide (E171) 
Macrogol 400 
 
6.2 Incompatibilities  
 
Not applicable. 
 
6.3 Shelf life  
 
4 years 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions.  
 
6.5 Nature and contents of container 
 
Cartons of 28, 56, 90 or 98 film-coated tablets in PVC/PVDC-aluminium/PVDC blisters. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Any unused product or waste material should be disposed of in accordance with local requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Pharmathen S.A.  
6, Dervenakion str.,  
15351 Pallini  
Attiki, Greece  
Tel.: +30 210 66 65 067 
 
 
8. MARKETING AUTHORISATION NUMBERS 
 
EU/1/12/765/001 
EU/1/12/765/002 
EU/1/12/765/007 
EU/1/12/765/010 
 

 
9. DATE OF FIRST AUTHORISATION / RENEWAL OF THE AUTHORISATION 
 
Date of first Authorization: 13 April 2012 
 
 
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 
 
Sabervel 150 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 150 mg of irbesartan 
 
Excipient with known effect:  
40 mg of lactose monohydrate per film-coated tablet  
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet. 
White, concave, round, film-coated tablet with 9 mm diameter. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications  
 
Sabervel is indicated in adults for the treatment of essential hypertension. 
It is also indicated for the treatment of renal disease in adult patients with hypertension and type 2 
diabetes mellitus as part of an antihypertensive medicinal product regimen (see sections 4.3, 4.4, 4.5 
and 5.1). 
 
4.2 Posology and method of administration 
 
Posology 
 
The usual recommended initial and maintenance dose is 150 mg once daily, with or without food. 
Sabervel at a dose of 150 mg once daily generally provides a better 24 hour blood pressure control 
than 75 mg. However, initiation of therapy with 75 mg could be considered, particularly in 
haemodialysed patients and in the elderly over 75 years. 
 
In patients insufficiently controlled with 150 mg once daily, the dose of Sabervel can be increased to 
300 mg, or other antihypertensive agents can be added (see sections 4.3, 4.4, 4.5 and 5.1). In 
particular, the addition of a diuretic such as hydrochlorothiazide has been shown to have an additive 
effect with Sabervel (see section 4.5). 
 
In hypertensive type 2 diabetic patients, therapy should be initiated at 150 mg irbesartan once daily 
and titrated up to 300 mg once daily as the preferred maintenance dose for treatment of renal disease. 
The demonstration of renal benefit of Sabervel in hypertensive type 2 diabetic patients is based on 
studies where irbesartan was used in addition to other antihypertensive agents, as needed, to reach 
target blood pressure (see sections 4.3, 4.4, 4.5 and 5.1). 
 
Special Populations 
 
Renal impairment: no dosage adjustment is necessary in patients with impaired renal function. A 
lower starting dose (75 mg) should be considered for patients undergoing haemodialysis (see section 
4.4). 
 
Hepatic impairment: no dosage adjustment is necessary in patients with mild to moderate hepatic 

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impairment. There is no clinical experience in patients with severe hepatic impairment. 
 
Elderly patients: although consideration should be given to initiating therapy with 75 mg in patients 
over 75 years of age, dosage adjustment is not usually necessary for the elderly. 
 
Paediatric population: the safety and efficacy of Sabervel in children aged 0 to 18 has not been 
established. Currently available data are described in section 4.8, 5.1 and 5.2 but no recommendation 
on a posology can be made. 
 
Method of Administration 
 
For oral use. 
 
4.3 Contraindications  
 
Hypersensitivity to the active substance, or to any of the excipients (see section 6.1).  
Second and third trimesters of pregnancy (see sections 4.4 and 4.6). 
 
The concomitant use of Sabervel with aliskiren-containing products is contraindicated in patients with 
diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m2) (see sections 4.5 and 5.1). 
 
4.4 Special warnings and precautions for use  
 
Intravascular volume depletion: symptomatic hypotension, especially after the first dose, may occur in 
patients who are volume and/or sodium depleted by vigorous diuretic therapy, dietary salt restriction, 
diarrhoea or vomiting. Such conditions should be corrected before the administration of Sabervel. 
 
Renovascular hypertension: there is an increased risk of severe hypotension and renal insufficiency 
when patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney 
are treated with medicinal products that affect the renin-angiotensin-aldosterone system. While this is 
not documented with Sabervel, a similar effect should be anticipated with angiotensin-II receptor 
antagonists. 
 
Renal impairment and kidney transplantation: when Sabervel is used in patients with impaired renal 
function, a periodic monitoring of potassium and creatinine serum levels is recommended. There is no 
experience regarding the administration of Sabervel in patients with a recent kidney transplantation. 
 
Hypertensive patients with type 2 diabetes and renal disease: the effects of irbesartan both on renal and 
cardiovascular events were not uniform across all subgroups, in an analysis carried out in the study 
with patients with advanced renal disease. In particular, they appeared less favourable in women and 
non-white subjects (see section 5.1). 
 
Dual blockade of the renin-angiotensin-aldosterone system (RAAS) 
There is evidence that the concomitant use of ACE-inhibitors, angiotensin II receptor blockers or 
aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including 
acute renal failure). Dual blockade of RAAS through the combined use of ACE-inhibitors, angiotensin 
II receptor blockers or aliskiren is therefore not recommended (see sections 4.5 and 5.1). 
If dual blockade therapy is considered absolutely necessary, this should only occur under specialist 
supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure. 
ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with 
diabetic nephropathy. 
 
Hyperkalaemia: as with other medicinal products that affect the renin-angiotensin-aldosterone system, 
hyperkalaemia may occur during the treatment with Sabervel, especially in the presence of renal 
impairment, overt proteinuria due to diabetic renal disease, and/or heart failure. Close monitoring of 
serum potassium in patients at risk is recommended (see section 4.5). 
 

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Lithium: the combination of lithium and Sabervel is not recommended (see section 4.5). 
 
Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy: as with other vasodilators, 
special caution is indicated in patients suffering from aortic or mitral stenosis, or obstructive 
hypertrophic cardiomyopathy. 
 
Primary aldosteronism: patients with primary aldosteronism generally will not respond to 
antihypertensive medicinal products acting through inhibition of the renin-angiotensin system. 
Therefore, the use of Sabervel is not recommended. 
 
General: in patients whose vascular tone and renal function depend predominantly on the activity of 
the renin-angiotensin-aldosterone system (e.g. patients with severe congestive heart failure or 
underlying renal disease, including renal artery stenosis), treatment with angiotensin converting 
enzyme inhibitors or angiotensin-II receptor antagonists that affect this system has been associated 
with acute hypotension, azotaemia, oliguria, or rarely acute renal failure. As with any antihypertensive 
agent, excessive blood pressure decrease in patients with ischaemic cardiopathy or ischaemic 
cardiovascular disease could result in a myocardial infarction or stroke. 
As observed for angiotensin converting enzyme inhibitors, irbesartan and the other angiotensin 
antagonists are apparently less effective in lowering blood pressure in black people than in non-blacks, 
possibly because of higher prevalence of low-renin states in the black hypertensive population (see 
section 5.1). 
 
Pregnancy: Angiotensin II Receptor Antagonists (AIIRAs) should not be initiated during pregnancy.  
Unless continued AIIRA therapy is considered essential, patients planning pregnancy should be 
changed to alternative antihypertensive treatments which have an established safety profile for use in 
pregnancy. When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, 
and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.6). 
 
Lactose: this medicinal product contains lactose. Patients with rare hereditary problems of galactose 
intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this 
medicinal product. 
 
Paediatric population: irbesartan has been studied in paediatric populations aged 6 to 16 years old but 
the current data are insufficient to support an extension of the use in children until further data become 
available (see sections 4.8, 5.1 and 5.2). 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Diuretics and other antihypertensive agents: other antihypertensive agents may increase the 
hypotensive effects of irbesartan; however  irbesartan has been safely administered with other 
antihypertensive agents, such as beta-blockers, long-acting calcium channel blockers, and thiazide 
diuretics. Prior treatment with high dose diuretics may result in volume depletion and a risk of 
hypotension when initiating therapy with Sabervel (see section 4.4). 
 
Clinical trial data has shown that dual blockade of the renin-angiotensin-aldosterone-system (RAAS) 
through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is associated 
with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal 
function (including acute renal failure) compared to the use of a single RAAS-acting agent (see 
sections 4.3, 4.4 and 5.1). 
 
Potassium supplements and potassium-sp 
aring diuretics: based on experience with the use of other medicinal products that affect the renin-
angiotensin system, concomitant use of potassium-sparing diuretics, potassium supplements, salt 
substitutes containing potassium or other medicinal products that may increase serum potassium levels 
(e.g. heparin) may lead to increases in serum potassium and is, therefore, not recommended (see 
section 4.4). 
 

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Lithium: reversible increases in serum lithium concentrations and toxicity have been reported during 
concomitant administration of lithium with angiotensin converting enzyme inhibitors. Similar effects 
have been very rarely reported with irbesartan so far. Therefore, this combination is not recommended 
(see section 4.4). If the combination proves necessary, careful monitoring of serum lithium levels is 
recommended. 
 
Non-steroidal anti-inflammatory drugs: when angiotensin II antagonists are administered 
simultaneously with non-steroidal anti-inflammatory drugs (i.e. selective COX-2 inhibitors, 
acetylsalicylic acid (> 3 g/day) and non-selective NSAIDs), attenuation of the antihypertensive effect 
may occur. 
As with ACE inhibitors, concomitant use of angiotensin II antagonists and NSAIDs may lead to an 
increased risk of worsening of renal function, including possible acute renal failure, and an increase in 
serum potassium, especially in patients with poor pre-existing renal function. The combination should 
be administered with caution, especially in the elderly. Patients should be adequately hydrated and 
consideration should be given to monitoring renal function after initiation of concomitant therapy, and 
periodically thereafter. 
 
Additional information on irbesartan interactions: in clinical studies, the pharmacokinetic of irbesartan 
is not affected by hydrochlorothiazide. Irbesartan is mainly metabolised by CYP2C9 and to a lesser 
extent by glucuronidation. No significant pharmacokinetic or pharmacodynamic interactions were 
observed when irbesartan was coadministered with warfarin, a medicinal product metabolised by 
CYP2C9. The effects of CYP2C9 inducers such as rifampicin on the pharmacokinetic of irbesartan 
have not been evaluated. The pharmacokinetic of digoxin was not altered by coadministration of 
irbesartan. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy: 
 
The use of AIIRAs is not recommended during the first trimester of pregnancy (see section 4.4). The 
use of AIIRAs is contraindicated during the second and third trimesters of pregnancy (see sections 4.3 
and 4.4). 
 
Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors 
during the first trimester of pregnancy has not been conclusive; however a small increase in risk 
cannot be excluded. Whilst there is no controlled epidemiological data on the risk with Angiotensin II 
Receptor Antagonists (AIIRAs), similar risks may exist for this class of drugs. Unless continued 
AIIRA therapy is considered essential, patients planning pregnancy should be changed to alternative 
antihypertensive treatments which have an established safety profile for use in pregnancy. When 
pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, and, if appropriate, 
alternative therapy should be started. 
 
Exposure to AIIRA therapy during the second and third trimesters is known to induce human 
fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal 
toxicity (renal failure, hypotension, hyperkalaemia). (See section 5.3). 
Should exposure to AIIRAs have occurred from the second trimester of pregnancy, ultrasound check 
of renal function and skull is recommended. 
Infants whose mothers have taken AIIRAs should be closely observed for hypotension (see sections 
4.3 and 4.4). 
 
Breast-feeding: 
 
Because no information is available regarding the use of Sabervel during breast-feeding, Sabervel is 
not recommended and alternative treatments with better established safety profiles during breast-
feeding are preferable, especially while nursing a newborn or preterm infant. 
 
It is unknown whether irbesartan or its metabolites are excreted in human milk. 

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Available pharmacodynamic/toxicological data in rats have shown excretion of irbesartan or its 
metabolites in milk (for details see 5.3). 
 
Fertility 
 
Irbesartan had no effect upon fertility of treated rats and their offspring up to the dose levels inducing 
the first signs of parental toxicity (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
No studies on the effects on the ability to drive and use machines have been performed. Based on its 
pharmacodynamic properties, irbesartan is unlikely to affect this ability. When driving vehicles or 
operating machines, it should be taken into account that dizziness or weariness may occur during 
treatment. 
 
4.8 Undesirable effects 
 
In placebo-controlled trials in patients with hypertension, the overall incidence of adverse events did 
not differ between the irbesartan (56.2%) and the placebo groups (56.5%). Discontinuation due to any 
clinical or laboratory adverse event was less frequent for irbesartan-treated patients (3.3%) than for 
placebo-treated patients (4.5%). The incidence of adverse events was not related to dose (in the 
recommended dose range), gender, age, race, or duration of treatment. 
 
In diabetic hypertensive patients with microalbuminuria and normal renal function, orthostatic 
dizziness and orthostatic hypotension were reported in 0.5% of the patients (i.e., uncommon) but in 
excess of placebo. 
 
The following table presents the adverse drug reactions that were reported in placebo-controlled trials 
in which 1,965 hypertensive patients received irbesartan. Terms marked with a star (*) refer to the 
adverse reactions that were additionally reported in > 2% of diabetic hypertensive patients with 
chronic renal insufficiency and overt proteinuria and in excess of placebo. 
 
The frequency of adverse reactions listed below is defined using the following convention: 
very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare 
(≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000). Within each frequency grouping, undesirable effects 
are presented in order of decreasing seriousness. 
 
Adverse reactions additionally reported from post–marketing experience are also listed. These adverse 
reactions are derived from spontaneous reports. 
 
Immune system disorders: 
Not known:  hypersensitivity reactions such as angioedema, rash, urticaria 
 
Metabolism and nutrition disorders: 
Not known:  hyperkalaemia 
 
Nervous system disorders: 
Common:  dizziness, orthostatic dizziness* 
Not known:  vertigo, headache 
 
Ear and labyrinth disorder: 
Not known:  tinnitus 
 
Cardiac disorders: 
Uncommon:  tachycardia 
 
Vascular disorders: 

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Common:  orthostatic hypotension* 
Uncommon:  flushing 
 
Respiratory, thoracic and mediastinal disorders: 
Uncommon:  cough 
 
Gastrointestinal disorders: 
Common:  nausea/vomiting 
Uncommon:  diarrhoea, dyspepsia/heartburn 
Not known:   dysgeusia 
 
Hepatobiliary disorders: 
Uncommon:  jaundice 
Not known:   hepatitis, abnormal liver function 
 
Skin and subcutaneous tissue disorders: 
Not known:   leukocytoclastic vasculitis 
 
Musculoskeletal and connective tissue disorders: 
Common:  musculoskeletal pain* 
Not known: arthralgia, myalgia (in some cases associated with increased plasma creatine kinase 

levels), muscle cramps 
 
Renal and urinary disorders: 
Not known:  impaired renal function including cases of renal failure in patients at risk (see 
section 4.4) 
 
Reproductive system and breast disorders: 
Uncommon:  sexual dysfunction 
 
General disorders and administration site conditions: 
Common:  fatigue 
Uncommon:  chest pain 
 
Investigations: 
Very common: Hyperkalaemia* occurred more often in diabetic patients treated with 

irbesartan than with placebo. In diabetic hypertensive patients with 
microalbuminuria and normal renal function, hyperkalaemia (≥ 5.5 
mEq/L) occurred in 29.4% of the patients in the irbesartan 300 mg group 
and 22% of the patients in the placebo group. In diabetic hypertensive 
patients with chronic renal insufficiency and overt proteinuria, 
hyperkalaemia (≥ 5.5 mEq/L) occurred in 46.3% of the patients in the 
irbesartan group and 26.3% of the patients in the placebo group. 

Common: significant increases in plasma creatine kinase were commonly observed 
(1.7%) in irbesartan treated subjects. None of these increases were 
associated with identifiable clinical musculoskeletal events. 
In 1.7% of hypertensive patients with advanced diabetic renal disease 
treated with irbesartan, a decrease in haemoglobin*, which was not 
clinically significant, has been observed. 

 
Paediatric population:  
In a randomised trial of 318 hypertensive children and adolescents aged 6 to 16 years, the following 
adverse reactions occurred in the 3-week double-blind phase: headache (7.9%), hypotension (2.2%), 
dizziness (1.9%), cough (0.9%). In the 26-week open-label period of this trial the most frequent 
laboratory abnormalities observed were creatinine increases (6.5%) and elevated CK values in 2% of 
child recipients. 
 

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4.9 Overdose 
 
Experience in adults exposed to doses of up to 900 mg/day for 8 weeks revealed no toxicity. The most 
likely manifestations of overdose are expected to be hypotension and tachycardia; bradycardia might 
also occur from overdose. No specific information is available on the treatment of overdose with 
Sabervel. The patient should be closely monitored, and the treatment should be symptomatic and 
supportive. Suggested measures include induction of emesis and/or gastric lavage. Activated charcoal 
may be useful in the treatment of overdose. Irbesartan is not removed by haemodialysis. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Angiotensin-II antagonists, plain.  
ATC code: C09C A04. 
 
Mechanism of action: Irbesartan is a potent, orally active, selective angiotensin-II receptor (type AT1) 
antagonist. It is expected to block all actions of angiotensin-II mediated by the AT1 receptor, 
regardless of the source or route of synthesis of angiotensin-II. The selective antagonism of the 
angiotensin-II (AT1) receptors results in increases in plasma renin levels and angiotensin-II levels, and 
a decrease in plasma aldosterone concentration. Serum potassium levels are not significantly affected 
by irbesartan alone at the recommended doses. Irbesartan does not inhibit ACE (kininase-II), an 
enzyme which generates angiotensin-II and also degrades bradykinin into inactive metabolites. 
 
Irbesartan does not require metabolic activation for its activity.  
 
Clinical efficacy: 
Hypertension 
Irbesartan lowers blood pressure with minimal change in heart rate. The decrease in blood pressure is 
dose-related for once a day doses with a tendency towards plateau at doses above 300 mg. Doses of 
150-300 mg once daily lower supine or seated blood pressures at trough (i.e. 24 hours after dosing) by 
an average of 8-13/5-8 mm Hg (systolic/diastolic) greater than those associated with placebo. 
Peak reduction of blood pressure is achieved within 3-6 hours after administration and the blood 
pressure lowering effect is maintained for at least 24 hours. At 24 hours the reduction of blood 
pressure was 60-70% of the corresponding peak diastolic and systolic responses at the recommended 
doses. Once daily dosing with 150 mg produced trough and mean 24 hour responses similar to twice 
daily dosing on the same total dose. 
 
The blood pressure lowering effect of irbesartan is evident within 1-2 weeks, with the maximal effect 
occurring by 4-6 weeks after start of therapy. The antihypertensive effects are maintained during long 
term therapy. After withdrawal of therapy, blood pressure gradually returns toward baseline. Rebound 
hypertension has not been observed. 
The blood pressure lowering effects of irbesartan and thiazide-type diuretics are additive. In patients 
not adequately controlled by irbesartan alone, the addition of a low dose of hydrochlorothiazide 
(12.5 mg) to irbesartan once daily results in a further placebo-adjusted blood pressure reduction at 
trough of 7-10/3-6 mm Hg (systolic/diastolic). 
The efficacy of irbesartan is not influenced by age or gender. As is the case with other medicinal 
products that affect the renin-angiotensin system, black hypertensive patients have notably less 
response to irbesartan monotherapy. When irbesartan is administered concomitantly with a low dose of 
hydrochlorothiazide (e.g. 12.5 mg daily), the antihypertensive response in black patients approaches 
that of white patients. 
There is no clinically important effect on serum uric acid or urinary uric acid secretion. 
 
Paediatric population  
Reduction of blood pressure with 0.5 mg/kg (low), 1.5 mg/kg (medium) and 4.5 mg/kg (high) target 
titrated doses of irbesartan was evaluated in 318 hypertensive or at risk (diabetic, family history of 

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hypertension) children and adolescents aged 6 to 16 years over a three week period. At the end of the 
three weeks the mean reduction from baseline in the primary efficacy variable, trough seated systolic 
blood pressure (SeSBP) was 11.7 mmHg (low dose), 9.3 mmHg (medium dose), 13.2 mmHg (high 
dose). No significant difference was apparent between these doses. Adjusted mean change of trough 
seated diastolic blood pressure (SeDBP) was as follows: 3.8 mmHg (low dose), 3.2 mmHg (medium 
dose), 5.6 mmHg (high dose). Over a subsequent two week period where patients were re-randomized 
to either active medicinal product or placebo, patients on placebo had increases of 2.4 and 2.0 mmHg 
in SeSBP and SeDBP compared to +0.1 and -0.3 mmHg changes respectively in those on all doses of 
irbesartan (see section 4.2). 
 
Hypertension and type 2 diabetes with renal disease 
The “Irbesartan Diabetic Nephropathy Trial (IDNT)” shows that irbesartan decreases the progression 
of renal disease in patients with chronic renal insufficiency and overt proteinuria. IDNT was a double 
blind, controlled, morbidity and mortality trial comparing irbesartan, amlodipine and placebo. In 1,715 
hypertensive patients with type 2 diabetes, proteinuria ≥ 900 mg/day and serum creatinine ranging 
from 1.0-3.0 mg/dl, the long-term effects (mean 2.6 years) of irbesartan on the progression of renal 
disease and all-cause mortality were examined. Patients were titrated from 75 mg to a maintenance 
dose of 300 mg irbesartan, from 2.5 mg to 10 mg amlodipine, or placebo as tolerated.  
Patients in all treatment groups typically received between 2 and 4 antihypertensive agents (e.g., 
diuretics, beta blockers, alpha blockers) to reach a predefined blood pressure goal of ≤ 135/85 mmHg 
or a 10 mmHg reduction in systolic pressure if baseline was > 160 mmHg. Sixty per cent (60%) of 
patients in the placebo group reached this target blood pressure whereas this figure was 76% and 78% 
in the irbesartan and amlodipine groups respectively.  
Irbesartan significantly reduced the relative risk in the primary combined endpoint of doubling serum 
creatinine, end-stage renal disease (ESRD) or all-cause mortality. Approximately 33% of patients in 
the irbesartan group reached the primary renal composite endpoint compared to 39% and 41% in the 
placebo and amlodipine groups [20% relative risk reduction versus placebo (p = 0.024) and 23% 
relative risk reduction compared to amlodipine (p = 0.006)]. When the individual components of the 
primary endpoint were analysed, no effect in all cause mortality was observed, while a positive trend 
in the reduction in ESRD and a significant reduction in doubling of serum creatinine were observed. 
 
Subgroups consisting of gender, race, age, duration of diabetes, baseline blood pressure, serum 
creatinine, and albumin excretion rate were assessed for treatment effect. In the female and black 
subgroups which represented 32% and 26% of the overall study population respectively, a renal 
benefit was not evident, although the confidence intervals do not exclude it. As for the secondary 
endpoint of fatal and non-fatal cardiovascular events, there was no difference among the three groups 
in the overall population, although an increased incidence of non-fatal MI was seen for women and a 
decreased incidence of non-fatal MI was seen in males in the irbesartan group versus the placebo-
based regimen. An increased incidence of non-fatal MI and stroke was seen in females in the 
irbesartan-based regimen versus the amlodipine-based regimen, while hospitalization due to heart 
failure was reduced in the overall population. However, no proper explanation for these findings in 
women has been identified. 
 
The study of the “Effects of Irbesartan on Microalbuminuria in Hypertensive Patients with type 2 
Diabetes Mellitus (IRMA 2)” shows that irbesartan 300 mg delays progression to overt proteinuria in 
patients with microalbuminuria. IRMA 2 was a placebo-controlled double blind morbidity study in 
590 patients with type 2 diabetes, microalbuminuria (30-300 mg/day) and normal renal function 
(serum creatinine ≤ 1.5 mg/dl in males and < 1.1 mg/dl in females). The study examined the long-term 
effects (2 years) of irbesartan on the progression to clinical (overt) proteinuria (urinary albumin 
excretion rate (UAER) > 300 mg/day, and an increase in UAER of at least 30% from baseline). The 
predefined blood pressure goal was ≤ 135/85 mmHg. Additional antihypertensive agents (excluding 
ACE inhibitors, angiotensin II receptor antagonists and dihydropyridine calcium blockers) were added 
as needed to help achieve the blood pressure goal. While similar blood pressure was achieved in all 
treatment groups, fewer subjects in the irbesartan 300 mg group (5.2%) than in the placebo (14.9%) or 
in the irbesartan 150 mg group (9.7%) reached the endpoint of overt proteinuria, demonstrating a 70% 
relative risk reduction versus placebo (p = 0.0004) for the higher dose. An accompanying 
improvement in the glomerular filtration rate (GFR) was not observed during the first three months of 

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treatment. The slowing in the progression to clinical proteinuria was evident as early as three months 
and continued over the 2 year period. Regression to normoalbuminuria (< 30 mg/day) was more 
frequent in the irbesartan 300 mg group (34%) than in the placebo group (21%). 
 
Two large randomised, controlled trials (ONTARGET (ONgoing Telmisartan Alone and in 
combination with Ramipril Global Endpoint Trial) and VA NEPHRON-D (The Veterans Affairs 
Nephropathy in Diabetes)) have examined the use of the combination of an ACE-inhibitor with an 
angiotensin II receptor blocker. 
ONTARGET was a study conducted in patients with a history of cardiovascular or cerebrovascular 
disease, or type 2 diabetes mellitus accompanied by evidence of end-organ damage. VA NEPHRON-D 
was a study in patients with type 2 diabetes mellitus and diabetic nephropathy. 
These studies have shown no significant beneficial effect on renal and/or cardiovascular outcomes and 
mortality, while an increased risk of hyperkalaemia, acute kidney injury and/or hypotension as 
compared to monotherapy was observed. Given their similar pharmacodynamic properties, these 
results are also relevant for other ACE-inhibitors and angiotensin II receptor blockers. 
ACE-inhibitors and angiotensin II receptor blockers should therefore not be used concomitantly in 
patients with diabetic nephropathy. 
ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) 
was a study designed to test the benefit of adding aliskiren to a standard therapy of an ACE-inhibitor 
or an angiotensin II receptor blocker in patients with type 2 diabetes mellitus and chronic kidney 
disease, cardiovascular disease, or both. The study was terminated early because of an increased risk 
of adverse outcomes. Cardiovascular death and stroke were both numerically more frequent in the 
aliskiren group than in the placebo group and adverse events and serious adverse events of interest 
(hyperkalaemia, hypotension and renal dysfunction) were more frequently reported in the aliskiren 
group than in the placebo group. 
 
5.2 Pharmacokinetic properties 
 
After oral administration, irbesartan is well absorbed: studies of absolute bioavailability gave values of 
approximately 60-80%. Concomitant food intake does not significantly influence the bioavailability of 
irbesartan. Plasma protein binding is approximately 96%, with negligible binding to cellular blood 
components. The volume of distribution is 53 - 93 litres. Following oral or intravenous administration 
of 14C irbesartan, 80-85% of the circulating plasma radioactivity is attributable to unchanged 
irbesartan. Irbesartan is metabolised by the liver via glucuronide conjugation and oxidation. The major 
circulating metabolite is irbesartan glucuronide (approximately 6%). In vitro studies indicate that 
irbesartan is primarily oxidised by the cytochrome P450 enzyme CYP2C9; isoenzyme CYP3A4 has 
negligible effect. 
 
Irbesartan exhibits linear and dose proportional pharmacokinetics over the dose range of 10 to 600 mg. 
A less than proportional increase in oral absorption at doses beyond 600 mg (twice the maximal 
recommended dose) was observed; the mechanism for this is unknown. Peak plasma concentrations 
are attained at 1.5 - 2 hours after oral administration. The total body and renal clearance are 157 - 176 
and 3 - 3.5 ml/min, respectively. The terminal elimination half-life of irbesartan is 11 - 15 hours. 
Steady-state plasma concentrations are attained within 3 days after initiation of a once-daily dosing 
regimen. Limited accumulation of irbesartan (< 20%) is observed in plasma upon repeated once-daily 
dosing. In a study, somewhat higher plasma concentrations of irbesartan were observed in female 
hypertensive patients. However, there was no difference in the half-life and accumulation of 
irbesartan. No dosage adjustment is necessary in female patients. Irbesartan AUC and Cmax values 
were also somewhat greater in elderly subjects (≥ 65 years) than those of young subjects (18 - 40 
years). However the terminal half-life was not significantly altered. No dosage adjustment is necessary 
in elderly patients. 
 
Irbesartan and its metabolites are eliminated by both biliary and renal pathways. After either oral or IV 
administration of 14C irbesartan, about 20% of the radioactivity is recovered in the urine, and the 
remainder in the faeces. Less than 2% of the dose is excreted in the urine as unchanged irbesartan. 
 
Paediatric population 

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The pharmacokinetics of irbesartan were evaluated in 23 hypertensive children after the administration 
of single and multiple daily doses of irbesartan (2 mg/kg) up to a maximum daily dose of 150 mg for 
four weeks. Of those 23 children, 21 were evaluable for comparison of pharmacokinetics with adults 
(twelve children over 12 years, nine children between 6 and 12 years). Results showed that Cmax, 
AUC and clearance rates were comparable to those observed in adult patients receiving 150 mg 
irbesartan daily. A limited accumulation of irbesartan (18%) in plasma was observed upon repeated 
once daily dosing. 
 
Renal impairment: in patients with renal impairment or those undergoing haemodialysis, the 
pharmacokinetic parameters of irbesartan are not significantly altered. Irbesartan is not removed by 
haemodialysis. 
 
Hepatic impairment: in patients with mild to moderate cirrhosis, the pharmacokinetic parameters of 
irbesartan are not significantly altered. 
Studies have not been performed in patients with severe hepatic impairment. 
 
5.3 Preclinical safety data 
 
There was no evidence of abnormal systemic or target organ toxicity at clinically relevant doses. In 
non-clinical safety studies, high doses of irbesartan (≥ 250 mg/kg/day in rats and ≥ 100 mg/kg/day in 
macaques) caused a reduction of red blood cell parameters (erythrocytes, haemoglobin, haematocrit). 
At very high doses (≥ 500 mg/kg/day) degenerative changes in the kidney (such as interstitial 
nephritis, tubular distension, basophilic tubules, increased plasma concentrations of urea and 
creatinine) were induced by irbesartan in the rat and the macaque and are considered secondary to the 
hypotensive effects of the medicinal product which led to decreased renal perfusion. Furthermore, 
irbesartan induced hyperplasia/hypertrophy of the juxtaglomerular cells (in rats at ≥ 90 mg/kg/day, in 
macaques at ≥ 10 mg/kg/day). All of these changes were considered to be caused by the 
pharmacological action of irbesartan. For therapeutic doses of irbesartan in humans, the hyperplasia/ 
hypertrophy of the renal juxtaglomerular cells does not appear to have any relevance. 
 
There was no evidence of mutagenicity, clastogenicity or carcinogenicity. 
 
Fertility and reproductive performance were not affected in studies of male and female rats even at 
oral doses of irbesartan causing some parental toxicity (from 50 to 650 mg/kg/day), including 
mortality at the highest dose. No significant effects on the number of corpora lutea, implants, or live 
fetuses were observed. Irbesartan did not affect survival, development, or reproduction of offspring. 
Studies in animals indicate that the radiolabeled irbesartan is detected in rat and rabbit fetuses. 
Irbesartan is excreted in the milk of lactating rats. 
 
Animal studies with irbesartan showed transient toxic effects (increased renal pelvic cavitation, 
hydroureter or subcutaneous oedema) in rat foetuses, which were resolved after birth. In rabbits, 
abortion or early resorption were noted at doses causing significant maternal toxicity, including 
mortality. No teratogenic effects were observed in the rat or rabbit. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core: 
Lactose monohydrate  
Microcrystalline cellulose  
Croscarmellose sodium  
Silica colloidal anhydrous 
Hypromellose 
Magnesium stearate. 
 

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Film-coating: 
Hypromellose  
Titanium dioxide (E171) 
Macrogol 400 
 
6.2 Incompatibilities  
 
Not applicable. 
 
6.3 Shelf life  
 
4 years 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions.  
 
6.5 Nature and contents of container 
 
Cartons of 28, 56, 90 or 98 film-coated tablets in PVC/PVDC-aluminium/PVDC blisters. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Any unused product or waste material should be disposed of in accordance with local requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Pharmathen S.A.  
6, Dervenakion str.,  
15351 Pallini  
Attiki, Greece  
Tel.: +30 210 66 65 067 
 
 
8. MARKETING AUTHORISATION NUMBERS 
 
EU/1/12/765/003 
EU/1/12/765/004 
EU/1/12/765/008 
EU/1/12/765/011 
 

 
 
9. DATE OF FIRST AUTHORISATION / RENEWAL OF THE AUTHORISATION 
 
Date of first Authorization: 13 April 2012 
 
 
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 
 
Sabervel 300 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 300 mg of irbesartan 
 
Excipient with known effect:  
80 mg of lactose monohydrate per film-coated tablet 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet. 
White, concave, round, film-coated tablet with 11 mm diameter.  
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications  
 
Sabervel is indicated in adults for the treatment of essential hypertension. 
It is also indicated for the treatment of renal disease in adult patients with hypertension and type 2 
diabetes mellitus as part of an antihypertensive medicinal product regimen (see sections 4.3, 4.4, 4.5 
and 5.1). 
 
4.2 Posology and method of administration 
 
Posology 
 
The usual recommended initial and maintenance dose is 150 mg once daily, with or without food. 
Sabervel at a dose of 150 mg once daily generally provides a better 24 hour blood pressure control 
than 75 mg. However, initiation of therapy with 75 mg could be considered, particularly in 
haemodialysed patients and in the elderly over 75 years. 
 
In patients insufficiently controlled with 150 mg once daily, the dose of Sabervel can be increased to 
300 mg, or other antihypertensive agents can be added (see sections 4.3, 4.4, 4.5 and 5.1). In 
particular, the addition of a diuretic such as hydrochlorothiazide has been shown to have an additive 
effect with Sabervel (see section 4.5). 
 
In hypertensive type 2 diabetic patients, therapy should be initiated at 150 mg irbesartan once daily 
and titrated up to 300 mg once daily as the preferred maintenance dose for treatment of renal disease. 
The demonstration of renal benefit of Sabervel in hypertensive type 2 diabetic patients is based on 
studies where irbesartan was used in addition to other antihypertensive agents, as needed, to reach 
target blood pressure (see sections 4.3, 4.4, 4.5 and 5.1). 
 
Special Populations 
 
Renal impairment: no dosage adjustment is necessary in patients with impaired renal function. A 
lower starting dose (75 mg) should be considered for patients undergoing haemodialysis (see section 
4.4). 
 
Hepatic impairment: no dosage adjustment is necessary in patients with mild to moderate hepatic 

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impairment. There is no clinical experience in patients with severe hepatic impairment. 
 
Elderly patients: although consideration should be given to initiating therapy with 75 mg in patients 
over 75 years of age, dosage adjustment is not usually necessary for the elderly. 
 
Paediatric population: the safety and efficacy of Sabervel in children aged 0 to 18 has not been 
established. Currently available data are described in section 4.8, 5.1 and 5.2 but no recommendation 
on a posology can be made. 
 
Method of Administration 
 
For oral use. 
 
4.3 Contraindications  
 
Hypersensitivity to the active substance, or to any of the excipients (see section 6.1).  
Second and third trimesters of pregnancy (see sections 4.4 and 4.6). 
 
The concomitant use of Sabervel with aliskiren-containing products is contraindicated in patients with 
diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m2) (see sections 4.5 and 5.1). 
 
4.4 Special warnings and precautions for use  
 
Intravascular volume depletion: symptomatic hypotension, especially after the first dose, may occur in 
patients who are volume and/or sodium depleted by vigorous diuretic therapy, dietary salt restriction, 
diarrhoea or vomiting. Such conditions should be corrected before the administration of Sabervel. 
 
Renovascular hypertension: there is an increased risk of severe hypotension and renal insufficiency 
when patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney 
are treated with medicinal products that affect the renin-angiotensin-aldosterone system. While this is 
not documented with Sabervel, a similar effect should be anticipated with angiotensin-II receptor 
antagonists. 
 
Renal impairment and kidney transplantation: when Sabervel is used in patients with impaired renal 
function, a periodic monitoring of potassium and creatinine serum levels is recommended. There is no 
experience regarding the administration of Sabervel in patients with a recent kidney transplantation. 
 
Hypertensive patients with type 2 diabetes and renal disease: the effects of irbesartan both on renal and 
cardiovascular events were not uniform across all subgroups, in an analysis carried out in the study 
with patients with advanced renal disease. In particular, they appeared less favourable in women and 
non-white subjects (see section 5.1). 
 
Dual blockade of the renin-angiotensin-aldosterone system (RAAS) 
There is evidence that the concomitant use of ACE-inhibitors, angiotensin II receptor blockers or 
aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including 
acute renal failure). Dual blockade of RAAS through the combined use of ACE-inhibitors, angiotensin 
II receptor blockers or aliskiren is therefore not recommended (see sections 4.5 and 5.1). 
If dual blockade therapy is considered absolutely necessary, this should only occur under specialist 
supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure. 
ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with 
diabetic nephropathy. 
 
Hyperkalaemia: as with other medicinal products that affect the renin-angiotensin-aldosterone system, 
hyperkalaemia may occur during the treatment with Sabervel, especially in the presence of renal 
impairment, overt proteinuria due to diabetic renal disease, and/or heart failure. Close monitoring of 
serum potassium in patients at risk is recommended (see section 4.5). 
 

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Lithium: the combination of lithium and Sabervel is not recommended (see section 4.5). 
 
Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy: as with other vasodilators, 
special caution is indicated in patients suffering from aortic or mitral stenosis, or obstructive 
hypertrophic cardiomyopathy. 
 
Primary aldosteronism: patients with primary aldosteronism generally will not respond to 
antihypertensive medicinal products acting through inhibition of the renin-angiotensin system. 
Therefore, the use of Sabervel is not recommended. 
 
General: in patients whose vascular tone and renal function depend predominantly on the activity of 
the renin-angiotensin-aldosterone system (e.g. patients with severe congestive heart failure or 
underlying renal disease, including renal artery stenosis), treatment with angiotensin converting 
enzyme inhibitors or angiotensin-II receptor antagonists that affect this system has been associated 
with acute hypotension, azotaemia, oliguria, or rarely acute renal failure. As with any antihypertensive 
agent, excessive blood pressure decrease in patients with ischaemic cardiopathy or ischaemic 
cardiovascular disease could result in a myocardial infarction or stroke. 
As observed for angiotensin converting enzyme inhibitors, irbesartan and the other angiotensin 
antagonists are apparently less effective in lowering blood pressure in black people than in non-blacks, 
possibly because of higher prevalence of low-renin states in the black hypertensive population (see 
section 5.1). 
 
Pregnancy: Angiotensin II Receptor Antagonists (AIIRAs) should not be initiated during pregnancy.  
Unless continued AIIRA therapy is considered essential, patients planning pregnancy should be 
changed to alternative antihypertensive treatments which have an established safety profile for use in 
pregnancy. When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, 
and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.6). 
 
Lactose: this medicinal product contains lactose. Patients with rare hereditary problems of galactose 
intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this 
medicinal product. 
 
Paediatric population: irbesartan has been studied in paediatric populations aged 6 to 16 years old but 
the current data are insufficient to support an extension of the use in children until further data become 
available (see sections 4.8, 5.1 and 5.2). 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Diuretics and other antihypertensive agents: other antihypertensive agents may increase the 
hypotensive effects of irbesartan; however  irbesartan has been safely administered with other 
antihypertensive agents, such as beta-blockers, long-acting calcium channel blockers, and thiazide 
diuretics. Prior treatment with high dose diuretics may result in volume depletion and a risk of 
hypotension when initiating therapy with Sabervel (see section 4.4). 
 
Clinical trial data has shown that dual blockade of the renin-angiotensin-aldosterone-system (RAAS) 
through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is associated 
with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal 
function (including acute renal failure) compared to the use of a single RAAS-acting agent (see 
sections 4.3, 4.4 and 5.1). 
 
Potassium supplements and potassium-sparing diuretics: based on experience with the use of other 
medicinal products that affect the renin-angiotensin system, concomitant use of potassium-sparing 
diuretics, potassium supplements, salt substitutes containing potassium or other medicinal products 
that may increase serum potassium levels (e.g. heparin) may lead to increases in serum potassium and 
is, therefore, not recommended (see section 4.4). 
 
Lithium: reversible increases in serum lithium concentrations and toxicity have been reported during 

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concomitant administration of lithium with angiotensin converting enzyme inhibitors. Similar effects 
have been very rarely reported with irbesartan so far. Therefore, this combination is not recommended 
(see section 4.4). If the combination proves necessary, careful monitoring of serum lithium levels is 
recommended. 
 
Non-steroidal anti-inflammatory drugs: when angiotensin II antagonists are administered 
simultaneously with non-steroidal anti-inflammatory drugs (i.e. selective COX-2 inhibitors, 
acetylsalicylic acid (> 3 g/day) and non-selective NSAIDs), attenuation of the antihypertensive effect 
may occur. 
As with ACE inhibitors, concomitant use of angiotensin II antagonists and NSAIDs may lead to an 
increased risk of worsening of renal function, including possible acute renal failure, and an increase in 
serum potassium, especially in patients with poor pre-existing renal function. The combination should 
be administered with caution, especially in the elderly. Patients should be adequately hydrated and 
consideration should be given to monitoring renal function after initiation of concomitant therapy, and 
periodically thereafter. 
 
Additional information on irbesartan interactions: in clinical studies, the pharmacokinetic of irbesartan 
is not affected by hydrochlorothiazide. Irbesartan is mainly metabolised by CYP2C9 and to a lesser 
extent by glucuronidation. No significant pharmacokinetic or pharmacodynamic interactions were 
observed when irbesartan was coadministered with warfarin, a medicinal product metabolised by 
CYP2C9. The effects of CYP2C9 inducers such as rifampicin on the pharmacokinetic of irbesartan 
have not been evaluated. The pharmacokinetic of digoxin was not altered by coadministration of 
irbesartan. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy: 
 
The use of AIIRAs is not recommended during the first trimester of pregnancy (see section 4.4). The 
use of AIIRAs is contraindicated during the second and third trimesters of pregnancy (see sections 4.3 
and 4.4). 
 
Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors 
during the first trimester of pregnancy has not been conclusive; however a small increase in risk 
cannot be excluded. Whilst there is no controlled epidemiological data on the risk with Angiotensin II 
Receptor Antagonists (AIIRAs), similar risks may exist for this class of drugs. Unless continued 
AIIRA therapy is considered essential, patients planning pregnancy should be changed to alternative 
antihypertensive treatments which have an established safety profile for use in pregnancy. When 
pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, and, if appropriate, 
alternative therapy should be started. 
 
Exposure to AIIRA therapy during the second and third trimesters is known to induce human 
fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal 
toxicity (renal failure, hypotension, hyperkalaemia). (See section 5.3). 
Should exposure to AIIRAs have occurred from the second trimester of pregnancy, ultrasound check 
of renal function and skull is recommended. 
Infants whose mothers have taken AIIRAs should be closely observed for hypotension (see sections 
4.3 and 4.4). 
 
Breast-feeding: 
 
Because no information is available regarding the use of Sabervel during breast-feeding, Sabervel is 
not recommended and alternative treatments with better established safety profiles during breast-
feeding are preferable, especially while nursing a newborn or preterm infant. 
 
It is unknown whether irbesartan or its metabolites are excreted in human milk. 
Available pharmacodynamic/toxicological data in rats have shown excretion of irbesartan or its 

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metabolites in milk (for details see 5.3). 
 
Fertility 
 
Irbesartan had no effect upon fertility of treated rats and their offspring up to the dose levels inducing 
the first signs of parental toxicity (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
No studies on the effects on the ability to drive and use machines have been performed. Based on its 
pharmacodynamic properties, irbesartan is unlikely to affect this ability. When driving vehicles or 
operating machines, it should be taken into account that dizziness or weariness may occur during 
treatment. 
 
4.8 Undesirable effects 
 
In placebo-controlled trials in patients with hypertension, the overall incidence of adverse events did 
not differ between the irbesartan (56.2%) and the placebo groups (56.5%). Discontinuation due to any 
clinical or laboratory adverse event was less frequent for irbesartan-treated patients (3.3%) than for 
placebo-treated patients (4.5%). The incidence of adverse events was not related to dose (in the 
recommended dose range), gender, age, race, or duration of treatment. 
 
In diabetic hypertensive patients with microalbuminuria and normal renal function, orthostatic 
dizziness and orthostatic hypotension were reported in 0.5% of the patients (i.e., uncommon) but in 
excess of placebo. 
 
The following table presents the adverse drug reactions that were reported in placebo-controlled trials 
in which 1,965 hypertensive patients received irbesartan. Terms marked with a star (*) refer to the 
adverse reactions that were additionally reported in > 2% of diabetic hypertensive patients with 
chronic renal insufficiency and overt proteinuria and in excess of placebo. 
 
The frequency of adverse reactions listed below is defined using the following convention: 
very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare 
(≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000). Within each frequency grouping, undesirable effects 
are presented in order of decreasing seriousness. 
 
Adverse reactions additionally reported from post–marketing experience are also listed. These adverse 
reactions are derived from spontaneous reports. 
 
Immune system disorders: 
Not known:  hypersensitivity reactions such as angioedema, rash, urticaria 
 
Metabolism and nutrition disorders: 
Not known:  hyperkalaemia 
 
Nervous system disorders: 
Common:  dizziness, orthostatic dizziness* 
Not known:  vertigo, headache 
 
Ear and labyrinth disorder: 
Not known:  tinnitus 
 
Cardiac disorders: 
Uncommon:  tachycardia 
 
Vascular disorders: 
Common:  orthostatic hypotension* 

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Uncommon:  flushing 
 
Respiratory, thoracic and mediastinal disorders: 
Uncommon:  cough 
 
Gastrointestinal disorders: 
Common:  nausea/vomiting 
Uncommon:  diarrhoea, dyspepsia/heartburn 
Not known:   dysgeusia 
 
Hepatobiliary disorders: 
Uncommon:  jaundice 
Not known:   hepatitis, abnormal liver function 
 
Skin and subcutaneous tissue disorders: 
Not known:   leukocytoclastic vasculitis 
 
Musculoskeletal and connective tissue disorders: 
Common:  musculoskeletal pain* 
Not known: arthralgia, myalgia (in some cases associated with increased plasma creatine kinase 

levels), muscle cramps 
 
Renal and urinary disorders: 
Not known:  impaired renal function including cases of renal failure in patients at risk (see 
section 4.4) 
 
Reproductive system and breast disorders: 
Uncommon:  sexual dysfunction 
 
General disorders and administration site conditions: 
Common:  fatigue 
Uncommon:  chest pain 
 
Investigations: 
Very common: Hyperkalaemia* occurred more often in diabetic patients treated with 

irbesartan than with placebo. In diabetic hypertensive patients with 
microalbuminuria and normal renal function, hyperkalaemia (≥ 5.5 
mEq/L) occurred in 29.4% of the patients in the irbesartan 300 mg group 
and 22% of the patients in the placebo group. In diabetic hypertensive 
patients with chronic renal insufficiency and overt proteinuria, 
hyperkalaemia (≥ 5.5 mEq/L) occurred in 46.3% of the patients in the 
irbesartan group and 26.3% of the patients in the placebo group. 

Common: significant increases in plasma creatine kinase were commonly observed 
(1.7%) in irbesartan treated subjects. None of these increases were 
associated with identifiable clinical musculoskeletal events. 
In 1.7% of hypertensive patients with advanced diabetic renal disease 
treated with irbesartan, a decrease in haemoglobin*, which was not 
clinically significant, has been observed. 

 
 
Paediatric population:  
In a randomised trial of 318 hypertensive children and adolescents aged 6 to 16 years, the following 
adverse reactions occurred in the 3-week double-blind phase: headache (7.9%), hypotension (2.2%), 
dizziness (1.9%), cough (0.9%). In the 26-week open-label period of this trial the most frequent 
laboratory abnormalities observed were creatinine increases (6.5%) and elevated CK values in 2% of 
child recipients. 
 

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4.9 Overdose 
 
Experience in adults exposed to doses of up to 900 mg/day for 8 weeks revealed no toxicity. The most 
likely manifestations of overdose are expected to be hypotension and tachycardia; bradycardia might 
also occur from overdose. No specific information is available on the treatment of overdose with 
Sabervel. The patient should be closely monitored, and the treatment should be symptomatic and 
supportive. Suggested measures include induction of emesis and/or gastric lavage. Activated charcoal 
may be useful in the treatment of overdose. Irbesartan is not removed by haemodialysis. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Angiotensin-II antagonists, plain.  
ATC code: C09C A04. 
 
Mechanism of action: Irbesartan is a potent, orally active, selective angiotensin-II receptor (type AT1) 
antagonist. It is expected to block all actions of angiotensin-II mediated by the AT1 receptor, 
regardless of the source or route of synthesis of angiotensin-II. The selective antagonism of the 
angiotensin-II (AT1) receptors results in increases in plasma renin levels and angiotensin-II levels, and 
a decrease in plasma aldosterone concentration. Serum potassium levels are not significantly affected 
by irbesartan alone at the recommended doses. Irbesartan does not inhibit ACE (kininase-II), an 
enzyme which generates angiotensin-II and also degrades bradykinin into inactive metabolites. 
 
Irbesartan does not require metabolic activation for its activity.  
 
Clinical efficacy: 
Hypertension 
Irbesartan lowers blood pressure with minimal change in heart rate. The decrease in blood pressure is 
dose-related for once a day doses with a tendency towards plateau at doses above 300 mg. Doses of 
150-300 mg once daily lower supine or seated blood pressures at trough (i.e. 24 hours after dosing) by 
an average of 8-13/5-8 mm Hg (systolic/diastolic) greater than those associated with placebo. 
Peak reduction of blood pressure is achieved within 3-6 hours after administration and the blood 
pressure lowering effect is maintained for at least 24 hours. At 24 hours the reduction of blood 
pressure was 60-70% of the corresponding peak diastolic and systolic responses at the recommended 
doses. Once daily dosing with 150 mg produced trough and mean 24 hour responses similar to twice 
daily dosing on the same total dose. 
 
The blood pressure lowering effect of irbesartan is evident within 1-2 weeks, with the maximal effect 
occurring by 4-6 weeks after start of therapy. The antihypertensive effects are maintained during long 
term therapy. After withdrawal of therapy, blood pressure gradually returns toward baseline. Rebound 
hypertension has not been observed. 
The blood pressure lowering effects of irbesartan and thiazide-type diuretics are additive. In patients 
not adequately controlled by irbesartan alone, the addition of a low dose of hydrochlorothiazide 
(12.5 mg) to irbesartan once daily results in a further placebo-adjusted blood pressure reduction at 
trough of 7-10/3-6 mm Hg (systolic/diastolic). 
The efficacy of irbesartan is not influenced by age or gender. As is the case with other medicinal 
products that affect the renin-angiotensin system, black hypertensive patients have notably less 
response to irbesartan monotherapy. When irbesartan is administered concomitantly with a low dose of 
hydrochlorothiazide (e.g. 12.5 mg daily), the antihypertensive response in black patients approaches 
that of white patients. 
There is no clinically important effect on serum uric acid or urinary uric acid secretion. 
 
Paediatric population  
Reduction of blood pressure with 0.5 mg/kg (low), 1.5 mg/kg (medium) and 4.5 mg/kg (high) target 
titrated doses of irbesartan was evaluated in 318 hypertensive or at risk (diabetic, family history of 

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hypertension) children and adolescents aged 6 to 16 years over a three week period. At the end of the 
three weeks the mean reduction from baseline in the primary efficacy variable, trough seated systolic 
blood pressure (SeSBP) was 11.7 mmHg (low dose), 9.3 mmHg (medium dose), 13.2 mmHg (high 
dose). No significant difference was apparent between these doses. Adjusted mean change of trough 
seated diastolic blood pressure (SeDBP) was as follows: 3.8 mmHg (low dose), 3.2 mmHg (medium 
dose), 5.6 mmHg (high dose). Over a subsequent two week period where patients were re-randomized 
to either active medicinal product or placebo, patients on placebo had increases of 2.4 and 2.0 mmHg 
in SeSBP and SeDBP compared to +0.1 and -0.3 mmHg changes respectively in those on all doses of 
irbesartan (see section 4.2). 
 
Hypertension and type 2 diabetes with renal disease 
The “Irbesartan Diabetic Nephropathy Trial (IDNT)” shows that irbesartan decreases the progression 
of renal disease in patients with chronic renal insufficiency and overt proteinuria. IDNT was a double 
blind, controlled, morbidity and mortality trial comparing irbesartan, amlodipine and placebo. In 1,715 
hypertensive patients with type 2 diabetes, proteinuria ≥ 900 mg/day and serum creatinine ranging 
from 1.0-3.0 mg/dl, the long-term effects (mean 2.6 years) of irbesartan on the progression of renal 
disease and all-cause mortality were examined. Patients were titrated from 75 mg to a maintenance 
dose of 300 mg irbesartan, from 2.5 mg to 10 mg amlodipine, or placebo as tolerated.  
Patients in all treatment groups typically received between 2 and 4 antihypertensive agents (e.g., 
diuretics, beta blockers, alpha blockers) to reach a predefined blood pressure goal of ≤ 135/85 mmHg 
or a 10 mmHg reduction in systolic pressure if baseline was > 160 mmHg. Sixty per cent (60%) of 
patients in the placebo group reached this target blood pressure whereas this figure was 76% and 78% 
in the irbesartan and amlodipine groups respectively.  
Irbesartan significantly reduced the relative risk in the primary combined endpoint of doubling serum 
creatinine, end-stage renal disease (ESRD) or all-cause mortality. Approximately 33% of patients in 
the irbesartan group reached the primary renal composite endpoint compared to 39% and 41% in the 
placebo and amlodipine groups [20% relative risk reduction versus placebo (p = 0.024) and 23% 
relative risk reduction compared to amlodipine (p = 0.006)]. When the individual components of the 
primary endpoint were analysed, no effect in all cause mortality was observed, while a positive trend 
in the reduction in ESRD and a significant reduction in doubling of serum creatinine were observed. 
 
Subgroups consisting of gender, race, age, duration of diabetes, baseline blood pressure, serum 
creatinine, and albumin excretion rate were assessed for treatment effect. In the female and black 
subgroups which represented 32% and 26% of the overall study population respectively, a renal 
benefit was not evident, although the confidence intervals do not exclude it. As for the secondary 
endpoint of fatal and non-fatal cardiovascular events, there was no difference among the three groups 
in the overall population, although an increased incidence of non-fatal MI was seen for women and a 
decreased incidence of non-fatal MI was seen in males in the irbesartan group versus the placebo-
based regimen. An increased incidence of non-fatal MI and stroke was seen in females in the 
irbesartan-based regimen versus the amlodipine-based regimen, while hospitalization due to heart 
failure was reduced in the overall population. However, no proper explanation for these findings in 
women has been identified. 
 
The study of the “Effects of Irbesartan on Microalbuminuria in Hypertensive Patients with type 2 
Diabetes Mellitus (IRMA 2)” shows that irbesartan 300 mg delays progression to overt proteinuria in 
patients with microalbuminuria. IRMA 2 was a placebo-controlled double blind morbidity study in 
590 patients with type 2 diabetes, microalbuminuria (30-300 mg/day) and normal renal function 
(serum creatinine ≤ 1.5 mg/dl in males and < 1.1 mg/dl in females). The study examined the long-term 
effects (2 years) of irbesartan on the progression to clinical (overt) proteinuria (urinary albumin 
excretion rate (UAER) > 300 mg/day, and an increase in UAER of at least 30% from baseline). The 
predefined blood pressure goal was ≤ 135/85 mmHg. Additional antihypertensive agents (excluding 
ACE inhibitors, angiotensin II receptor antagonists and dihydropyridine calcium blockers) were added 
as needed to help achieve the blood pressure goal. While similar blood pressure was achieved in all 
treatment groups, fewer subjects in the irbesartan 300 mg group (5.2%) than in the placebo (14.9%) or 
in the irbesartan 150 mg group (9.7%) reached the endpoint of overt proteinuria, demonstrating a 70% 
relative risk reduction versus placebo (p = 0.0004) for the higher dose. An accompanying 
improvement in the glomerular filtration rate (GFR) was not observed during the first three months of 

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treatment. The slowing in the progression to clinical proteinuria was evident as early as three months 
and continued over the 2 year period. Regression to normoalbuminuria (< 30 mg/day) was more 
frequent in the irbesartan 300 mg group (34%) than in the placebo group (21%). 
 
Two large randomised, controlled trials (ONTARGET (ONgoing Telmisartan Alone and in 
combination with Ramipril Global Endpoint Trial) and VA NEPHRON-D (The Veterans Affairs 
Nephropathy in Diabetes)) have examined the use of the combination of an ACE-inhibitor with an 
angiotensin II receptor blocker. 
ONTARGET was a study conducted in patients with a history of cardiovascular or cerebrovascular 
disease, or type 2 diabetes mellitus accompanied by evidence of end-organ damage. VA NEPHRON-D 
was a study in patients with type 2 diabetes mellitus and diabetic nephropathy. 
These studies have shown no significant beneficial effect on renal and/or cardiovascular outcomes and 
mortality, while an increased risk of hyperkalaemia, acute kidney injury and/or hypotension as 
compared to monotherapy was observed. Given their similar pharmacodynamic properties, these 
results are also relevant for other ACE-inhibitors and angiotensin II receptor blockers. 
ACE-inhibitors and angiotensin II receptor blockers should therefore not be used concomitantly in 
patients with diabetic nephropathy. 
ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) 
was a study designed to test the benefit of adding aliskiren to a standard therapy of an ACE-inhibitor 
or an angiotensin II receptor blocker in patients with type 2 diabetes mellitus and chronic kidney 
disease, cardiovascular disease, or both. The study was terminated early because of an increased risk 
of adverse outcomes. Cardiovascular death and stroke were both numerically more frequent in the 
aliskiren group than in the placebo group and adverse events and serious adverse events of interest 
(hyperkalaemia, hypotension and renal dysfunction) were more frequently reported in the aliskiren 
group than in the placebo group. 
 
5.2 Pharmacokinetic properties 
 
After oral administration, irbesartan is well absorbed: studies of absolute bioavailability gave values of 
approximately 60-80%. Concomitant food intake does not significantly influence the bioavailability of 
irbesartan. Plasma protein binding is approximately 96%, with negligible binding to cellular blood 
components. The volume of distribution is 53 - 93 litres. Following oral or intravenous administration 
of 14C irbesartan, 80-85% of the circulating plasma radioactivity is attributable to unchanged 
irbesartan. Irbesartan is metabolised by the liver via glucuronide conjugation and oxidation. The major 
circulating metabolite is irbesartan glucuronide (approximately 6%). In vitro studies indicate that 
irbesartan is primarily oxidised by the cytochrome P450 enzyme CYP2C9; isoenzyme CYP3A4 has 
negligible effect. 
 
Irbesartan exhibits linear and dose proportional pharmacokinetics over the dose range of 10 to 600 mg. 
A less than proportional increase in oral absorption at doses beyond 600 mg (twice the maximal 
recommended dose) was observed; the mechanism for this is unknown. Peak plasma concentrations 
are attained at 1.5 - 2 hours after oral administration. The total body and renal clearance are 157 - 176 
and 3 - 3.5 ml/min, respectively. The terminal elimination half-life of irbesartan is 11 - 15 hours. 
Steady-state plasma concentrations are attained within 3 days after initiation of a once-daily dosing 
regimen. Limited accumulation of irbesartan (< 20%) is observed in plasma upon repeated once-daily 
dosing. In a study, somewhat higher plasma concentrations of irbesartan were observed in female 
hypertensive patients. However, there was no difference in the half-life and accumulation of 
irbesartan. No dosage adjustment is necessary in female patients. Irbesartan AUC and Cmax values 
were also somewhat greater in elderly subjects (≥ 65 years) than those of young subjects (18 - 40 
years). However the terminal half-life was not significantly altered. No dosage adjustment is necessary 
in elderly patients. 
 
Irbesartan and its metabolites are eliminated by both biliary and renal pathways. After either oral or IV 
administration of 14C irbesartan, about 20% of the radioactivity is recovered in the urine, and the 
remainder in the faeces. Less than 2% of the dose is excreted in the urine as unchanged irbesartan. 
 
Paediatric population 

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The pharmacokinetics of irbesartan were evaluated in 23 hypertensive children after the administration 
of single and multiple daily doses of irbesartan (2 mg/kg) up to a maximum daily dose of 150 mg for 
four weeks. Of those 23 children, 21 were evaluable for comparison of pharmacokinetics with adults 
(twelve children over 12 years, nine children between 6 and 12 years). Results showed that Cmax, 
AUC and clearance rates were comparable to those observed in adult patients receiving 150 mg 
irbesartan daily. A limited accumulation of irbesartan (18%) in plasma was observed upon repeated 
once daily dosing. 
 
Renal impairment: in patients with renal impairment or those undergoing haemodialysis, the 
pharmacokinetic parameters of irbesartan are not significantly altered. Irbesartan is not removed by 
haemodialysis. 
 
Hepatic impairment: in patients with mild to moderate cirrhosis, the pharmacokinetic parameters of 
irbesartan are not significantly altered. 
Studies have not been performed in patients with severe hepatic impairment. 
 
5.3 Preclinical safety data 
 
There was no evidence of abnormal systemic or target organ toxicity at clinically relevant doses. In 
non-clinical safety studies, high doses of irbesartan (≥ 250 mg/kg/day in rats and ≥ 100 mg/kg/day in 
macaques) caused a reduction of red blood cell parameters (erythrocytes, haemoglobin, haematocrit). 
At very high doses (≥ 500 mg/kg/day) degenerative changes in the kidney (such as interstitial 
nephritis, tubular distension, basophilic tubules, increased plasma concentrations of urea and 
creatinine) were induced by irbesartan in the rat and the macaque and are considered secondary to the 
hypotensive effects of the medicinal product which led to decreased renal perfusion. Furthermore, 
irbesartan induced hyperplasia/hypertrophy of the juxtaglomerular cells (in rats at ≥ 90 mg/kg/day, in 
macaques at ≥ 10 mg/kg/day). All of these changes were considered to be caused by the 
pharmacological action of irbesartan. For therapeutic doses of irbesartan in humans, the hyperplasia/ 
hypertrophy of the renal juxtaglomerular cells does not appear to have any relevance. 
 
There was no evidence of mutagenicity, clastogenicity or carcinogenicity. 
 
Fertility and reproductive performance were not affected in studies of male and female rats even at 
oral doses of irbesartan causing some parental toxicity (from 50 to 650 mg/kg/day), including 
mortality at the highest dose. No significant effects on the number of corpora lutea, implants, or live 
fetuses were observed. Irbesartan did not affect survival, development, or reproduction of offspring. 
Studies in animals indicate that the radiolabeled irbesartan is detected in rat and rabbit fetuses. 
Irbesartan is excreted in the milk of lactating rats. 
 
Animal studies with irbesartan showed transient toxic effects (increased renal pelvic cavitation, 
hydroureter or subcutaneous oedema) in rat foetuses, which were resolved after birth. In rabbits, 
abortion or early resorption were noted at doses causing significant maternal toxicity, including 
mortality. No teratogenic effects were observed in the rat or rabbit. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core: 
Lactose monohydrate  
Microcrystalline cellulose  
Croscarmellose sodium  
Silica colloidal anhydrous 
Hypromellose 
Magnesium stearate. 
 

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Film-coating: 
Hypromellose  
Titanium dioxide (E171) 
Macrogol 400 
 
6.2 Incompatibilities  
 
Not applicable. 
 
6.3 Shelf life  
 
4 years 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions.  
 
6.5 Nature and contents of container 
 
Cartons of 28, 56, 90 or 98 film-coated tablets in PVC/PVDC-aluminium/PVDC blisters. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Any unused product or waste material should be disposed of in accordance with local requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Pharmathen S.A.  
6, Dervenakion str.,  
15351 Pallini  
Attiki, Greece  
Tel.: +30 210 66 65 067 
 
 
8. MARKETING AUTHORISATION NUMBERS 
 
EU/1/12/765/005 
EU/1/12/765/006 
EU/1/12/765/009 
EU/1/12/765/012 

 
 
9. DATE OF FIRST AUTHORISATION / RENEWAL OF THE AUTHORISATION 
 
Date of first Authorization: 13 April 2012 
 
 
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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ANNEX II 
 

A. MANUFACTURERS 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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A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 
 

Name and address of the manufacturers responsible for batch release 

J. Uriach y Compañía, S.A. 
Av. Camí Reial, 51-57 
ES-08184 – Palau-solità i Plegamans 
Barcelona 
Spain 
 
Pharmathen S.A. 
6 Dervenakion str. 
15351 Pallini Attiki 
Greece 
 
Pharmathen International S.A. 
Industrial Park Sapes, 
Rodopi Prefecture, Block No 5, 
Rodopi 69300, 
Greece 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 
 
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) 
Not applicable 
 
PSURs 
The PSUR submission schedule should follow the PSUR submission schedule for the reference 
medicinal product. 
 

• CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 
Not applicable. 
 
•  
 

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ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 

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A. LABELLING 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Sabervel 75 mg film-coated tablets  
irbesartan 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 75 mg irbesartan 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: also contains lactose monohydrate. 
See leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
28 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  
 
 
9. SPECIAL STORAGE CONDITIONS 
 

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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 
 
Pharmathen S.A.  
6, Dervenakion str.,  
153 51 Pallini  
Attiki, Greece 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/12/765/001 
EU/1/12/765/002 
EU/1/12/765/007 
EU/1/12/765/010 
 

 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Sabervel 75 mg  

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Sabervel 75 mg film-coated tablets  
irbesartan  
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Pharmathen S.A. 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Sabervel 150 mg film-coated tablets  
irbesartan 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 150 mg irbesartan 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: also contains lactose monohydrate. 
See leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
28 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  
 
 
9. SPECIAL STORAGE CONDITIONS 

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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 
 
Pharmathen S.A.  
6, Dervenakion str.,  
153 51 Pallini  
Attiki, Greece 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
 
EU/1/12/765/003 
EU/1/12/765/004 
EU/1/12/765/008 
EU/1/12/765/011 
 

 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Sabervel 150 mg  

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Sabervel 150 mg film-coated tablets  
irbesartan 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Pharmathen S.A. 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Sabervel 300 mg film-coated tablets  
irbesartan 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 300 mg irbesartan 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: also contains lactose monohydrate. 
See leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
28 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  
 
 
9. SPECIAL STORAGE CONDITIONS 
 

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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 
 
Pharmathen S.A.  
6, Dervenakion str.,  
153 51 Pallini  
Attiki, Greece 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/12/765/005 
EU/1/12/765/006 
EU/1/12/765/009 
EU/1/12/765/012 

 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Sabervel 300 mg  
 

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Sabervel 300 mg film-coated tablets  
irbesartan 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Pharmathen S.A. 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 

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B. PACKAGE LEAFLET 

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PACKAGE LEAFLET: INFORMATION FOR THE USER  
 

Sabervel 75 mg film-coated tablets 
irbesartan 

 
Read all of this leaflet carefully before you start taking this medicine. 
• 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. Do not pass it on to others. It may harm them, even 

if their symptoms are the same as yours. 
• If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 
 
In this leaflet: 
1. What Sabervel is and what it is used for 
2. Before you take Sabervel 
3. How to take Sabervel 
4. Possible side effects 
5. How to store Sabervel 
6. Further information 
 
 
1. WHAT SABERVEL IS AND WHAT IT IS USED FOR 
 
Sabervel belongs to a group of medicines known as angiotensin-II receptor antagonists. Angiotensin-II 
is a substance produced in the body which binds to receptors in blood vessels causing them to tighten. 
This results in an increase in blood pressure. Sabervel prevents the binding of angiotensin-II to these 
receptors, causing the blood vessels to relax and the blood pressure to lower. Sabervel slows the 
decrease of kidney function in patients with high blood pressure and type 2 diabetes. 
 
Sabervel is used in adult patients 
• to treat high blood pressure (essential hypertension) 
• to protect the kidney in patients with high blood pressure, type 2 diabetes and laboratory 

evidence of impaired kidney function. 
 
 
2. BEFORE YOU TAKE SABERVEL  
 
Do not take Sabervel 
• if you are allergic (hypersensitive) to irbesartan or any other ingredients of Sabervel 
• if you are more than 3 months pregnant. (It is also better to avoid Sabervel in early pregnancy 

– see pregnancy section) 
• if you have diabetes or impaired kidney function and you are treated with a blood pressure 

lowering medicine containing aliskiren. 
 
Warnings and precautions Tell your doctor if any of the following apply to you: 
• if you get excessive vomiting or diarrhoea 
• if you suffer from kidney problems  
• if you suffer from heart problems  
• if you receive Sabervel for diabetic kidney disease. In this case your doctor may perform 

regular blood tests, especially for measuring blood potassium levels in case of poor kidney 
function 

• if you are going to have an operation (surgery) or be given anaesthetics. 
• if you are taking any of the following medicines used to treat high blood pressure:  

- an ACE-inhibitor (for example enalapril, lisinopril, ramipril), in particular if you have 
diabetes-related kidney problems. 

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- aliskiren 
 
Your doctor may check your kidney function, blood pressure, and the amount of electrolytes (e.g. 
potassium) in your blood at regular intervals. 
 
See also information under the heading “Do not take Sabervel”. 
 
You must tell your doctor if you think you are (or might become) pregnant. Sabervel is not 
recommended in early pregnancy, and must not be taken if you are more than 3 months pregnant, as it 
may cause serious harm to your baby if used at that stage (see pregnancy section). 
 
Use in Children 
This medicine should not be used in children and adolescents (under 18 years) because the safety and 
efficacy have not yet been fully established. 
 
Other medicines and Sabervel 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
 
Your doctor may need to change your dose and/or to take other precautions: 
If you are taking an ACE-inhibitor or aliskiren (see also information under the headings “Do not take 
Sabervel” and “Warnings and precautions”). 
 
You may need to have blood checks if you take: 
• potassium supplements 
• salt substitutes containing potassium 
• potassium-sparing medicines (such as certain diuretics) 
• medicines containing lithium 
 
If you take certain painkillers, called non-steroidal anti-inflammatory drugs, the effect of irbesartan 
may be reduced. 
 
Taking Sabervel with food and drink 
Sabervel can be taken with or without food. 
 
Pregnancy and breast-feeding 
Pregnancy 
You must tell your doctor if you think you are (or might become) pregnant. Your doctor will normally 
advise you to stop taking Sabervel before you become pregnant or as soon as you know you are 
pregnant and will advise you to take another medicine instead of Sabervel. Sabervel is not 
recommended in early pregnancy, and must not be taken when more than 3 months pregnant, as it may 
cause serious harm to your baby if used after the third month of pregnancy. 
 
Breast-feeding 
Tell your doctor if you are breast-feeding or about to start breast-feeding. Sabervel is not 
recommended for mothers who are breast-feeding, and your doctor may choose another treatment for 
you if you wish to breast-feed, especially if your baby is newborn, or was born prematurely. 
 
Driving and using machines 
No studies on the effects on the ability to drive and use machines have been performed. Sabervel is 
unlikely to affect your ability to drive or use machines. However, occasionally dizziness or weariness 
may occur during treatment of high blood pressure. If you experience these, talk to your doctor before 
attempting to drive or use machines. 
 
Important information about some of the ingredients of Sabervel 
Sabervel contains lactose. If you have been told by your doctor that you have an intolerance to some 
sugars (e.g. lactose), contact your doctor before taking this medicine. 

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3. HOW TO TAKE SABERVEL 
 
Always take Sabervel exactly as your doctor has told you. You should check with your doctor or 
pharmacist if you are not sure. 
 
Method of administration 
Sabervel is for oral use . Swallow the tablets with a sufficient amount of fluid (e.g. one glass of water). 
You can take Sabervel with or without food. Try to take your daily dose at about the same time each 
day. It is important that you continue to take Sabervel until your doctor tells you otherwise. 
 
• Patients with high blood pressure 

The usual dose is 150 mg once a day. The dose may later be increased to 300 mg once daily 
depending on blood pressure response. 

 
• Patients with high blood pressure and type 2 diabetes with kidney disease 

In patients with high blood pressure and type 2 diabetes, 300 mg once daily is the preferred 
maintenance dose for the treatment of associated kidney disease. 

 
The doctor may advise a lower dose, especially when starting treatment in certain patients such as 
those on haemodialysis, or those over the age of 75 years . 
 
The maximal blood pressure lowering effect should be reached 4-6 weeks after beginning treatment. 
 
If you take more Sabervel than you should: 
If you accidentally take too many tablets, contact your doctor immediately. 
 
Children should not take Sabervel 
Sabervel should not be given to children under 18 years of age. If a child swallows some tablets, 
contact your doctor immediately. 
 
If you forget to take Sabervel: 
If you accidentally miss a daily dose, just take the next dose as normal. Do not take a double dose to 
make up for a forgotten dose. 
 
If you have any further questions on the use of this product, ask your doctor or pharmacist. 
 
 
4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, Sabervel can cause side effects, although not everybody gets them. Some of these 
effects may be serious and may require medical attention. 
 
As with similar medicines, rare cases of allergic skin reactions (rash, urticaria), as well as localised 
swelling of the face, lips and/or tongue have been reported in patients taking irbesartan. If you get any 
of these symptoms or get short of breath, stop taking Sabervel and contact your doctor 
immediately. 
 
The frequency of the side effects listed below is defined using the following convention:  
Very common: at least 1 in 10 patients or more 
Common: at least 1 in 100 and less than 1 in 10 patients 
Uncommon: at least 1 in 1000 and less than 1 in 100 patientsSide effects reported in clinical studies 
for patients treated with  Irbesartan were: 
• Very common : if you suffer from high blood pressure and type 2 diabetes with kidney disease, 

blood tests may show an increased level of potassium. 
 

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• Common : dizziness, feeling sick/vomiting, fatigue and blood tests may show raised levels of an 
enzyme that measures the muscle and heart function (creatine kinase enzyme). In patients with 
high blood pressure and type 2 diabetes with kidney disease, dizziness when getting up from a 
lying or sitting position, low blood pressure when getting up from a lying or sitting position, 
pain in joints or muscles and decreased levels of a protein in the red blood cells (haemoglobin) 
were also reported. 

 
• Uncommon : heart rate increased, flushing, cough, diarrhoea, indigestion/heartburn, sexual 

dysfunction (problems with sexual performance), chest pain. 
 
Some side effects have been reported since marketing of Irbesartan Side effects where the frequency is 
not known are: feeling of spinning, headache, taste disturbance, ringing in the ears, muscle cramps, 
pain in joints and muscles, abnormal liver function, increased blood potassium levels, impaired kidney 
function, and inflammation of small blood vessels mainly affecting the skin (a condition known as 
leukocytoclastic vasculitis). 
Uncommon cases of jaundice (yellowing of the skin and/or whites of the eyes) have also been 
reported. 
 
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please 
tell your doctor or pharmacist. 
 
 
5. HOW TO STORE SABERVEL 
 
Keep out of the sight and reach of children. 
 
Do not use Sabervel after the expiry date which is stated on the carton and on the blister after EXP. 
The expiry date refers to the last day of that month. 
 
This medicinal product does not require any special storage conditions. 
 
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to 
dispose of medicines no longer required. These measures will help to protect the environment. 
 
 
6. FURTHER INFORMATION  
 
What Sabervel contains 
 
• The active substance is irbesartan. Each tablet of Sabervel 75 mg contains 75 mg irbesartan. 
• The other ingredients are:  

Tablet core: lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, silica 
colloidal anhydrous, hypromellose, magnesium stearate,  
Film-coating: hypromellose, titanium dioxide (E171), macrogol 400 

 
 
What Sabervel looks like and contents of the pack 
Sabervel 75 mg film-coated tablets are white, concave, round, film-coated tablets with 7 mm diameter.  
 
Sabervel 75mg film-coated tablets are supplied in blister packs of 28, 56, 90 or 98 film- coated tablets.  
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder: 
Pharmathen S.A,  
6 Dervenakion Str.,  
15351 Pallini, Attiki, Greece 

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Manufacturer: 
 
J. Uriach y Compañía, S.A. 
Av. Camí Reial, 51-57 
08184 – Palau-solità i Plegamans, Barcelona, Spain 
 
Pharmathen S.A,  
6 Dervenakion Str.,  
15351 Pallini, Attiki, Greece 
 
Pharmathen International S.A. 
Industrial Park Sapes,  
Rodopi Prefecture, Block No 5, Rodopi 69300, Greece 
 
For any information about this medicinal product, please contact the local representative of the 
Marketing Authorisation Holder. 
 
België/Belgique/Belgien 
Pharmathen S.A. 
Tél/Tel: +30 210 66 65 067 
 

Lietuva 
Portfarma ehf. 
Tel: +354 534 4030  
 

България  
Pharmathen S.A. 
Teл.: +30 210 66 65 067 
 

Luxembourg/Luxemburg 
Portfarma ehf. 
Tel: +354 534 4030 

Česká republika 
Pharmathen S.A. 
Tel: +30 210 66 65 067 
 

Magyarország  
Pharmathen S.A. 
Tel.: +30 210 66 65 067 
 

Danmark 
Portfarma ehf. 
Tlf: +354 534 4030 
 

Malta 
Pharmathen S.A. 
Tel: +30 210 66 65 067 
 

Deutschland 
Glenmark Arzneimittel GmbH 
Tel: +49 8142 44392 0 

Nederland 
Glenmark Generics B.V.   
Tel: 0031 20 5226030 
 

Eesti (Estonia) 
Portfarma ehf. 
Tel: +354 534 4030 
 

Norge 
Pharmathen S.A. 
Tlf: +30 210 66 65 067 
 

Ελλάδα 
Pharmathen Hellas S.A. 
Τηλ: +30 210 66 04 300 
 

Österreich  
Pharmathen S.A. 
Tel: +30 210 66 65 067 

España 
Pharmathen S.A. 
Tel: +30 210 66 65 067 
 

Polska 
Pharmathen S.A. 
Tel.: +30 210 66 65 067 

France 
Pharmathen S.A. 
Tél: +30 210 66 65 067 
 

Portugal 
Pharmathen S.A. 
Tel: +30 210 66 65 067 

Hrvatska 
Pharmathen S.A. 
Tel: +30 210 66 65 067 

România 
Pharmathen S.A. 
Tel: +30 210 66 65 067 

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Ireland 
Aspire Pharma Limited 
Tel: +44(0)1730 234527 

 
Slovenija 
Pharmathen S.A. 
Tel: +30 210 66 65 067 

 
Ísland 
Portfarma ehf. 
Tel: +354 534 4030 

 
Slovenská republika  
Pharmathen S.A. 
Tel: +30 210 66 65 067 

 
Italia 
Pharmathen S.A. 
Tel: +30 210 66 65 067 

 
Suomi/Finland 
Pharmathen S.A. 
Puh/Tel: +30 210 66 65 067 

 
Κύπρος 
C.V. MEDILINE LTD  
Τηλ: +357 25761699 
 

 
Sverige  
Pharmathen S.A. 
Tel: +30 210 66 65 067 
 

Latvija  
Portfarma ehf. 
Tel: +354 534 4030 
 

United Kingdom 
Aspire Pharma Limited 
Tel: +44(0)1730 234527 

 
This leaflet was last approved in 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 

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


PACKAGE LEAFLET: INFORMATION FOR THE USER  
 

Sabervel 150 mg film-coated tablets 
irbesartan 

 
Read all of this leaflet carefully before you start taking this medicine . 
• 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. Do not pass it on to others. It may harm them, even 

if their symptoms are the same as yours. 
• If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 
 
In this leaflet: 
1. What Sabervel is and what it is used for 
2. Before you take Sabervel 
3. How to take Sabervel 
4. Possible side effects 
5. How to store Sabervel 
6. Further information 
 
 
1. WHAT SABERVEL IS AND WHAT IT IS USED FOR 
 
Sabervel belongs to a group of medicines known as angiotensin-II receptor antagonists. Angiotensin-II 
is a substance produced in the body which binds to receptors in blood vessels causing them to tighten. 
This results in an increase in blood pressure. Sabervel prevents the binding of angiotensin-II to these 
receptors, causing the blood vessels to relax and the blood pressure to lower. Sabervel slows the 
decrease of kidney function in patients with high blood pressure and type 2 diabetes. 
 
Sabervel is used in adult patients 
• to treat high blood pressure (essential hypertension) 
• to protect the kidney in patients with high blood pressure, type 2 diabetes and laboratory 

evidence of impaired kidney function. 
 
 
2. BEFORE YOU TAKE SABERVEL  
 
Do not take Sabervel 
• if you are allergic (hypersensitive) to irbesartan or any other ingredients of Sabervel 
• if you are more than 3 months pregnant. (It is also better to avoid Sabervel in early pregnancy 

– see pregnancy section) 
• if you have diabetes or impaired kidney function and you are treated with a blood pressure 

lowering medicine containing aliskiren. 
 
Warning and precautions  
Tell your doctor if any of the following apply to you: 
• if you get excessive vomiting or diarrhoea 
• if you suffer from kidney problems  
• if you suffer from heart problems  
• if you receive Sabervel for diabetic kidney disease. In this case your doctor may perform 

regular blood tests, especially for measuring blood potassium levels in case of poor kidney 
function 

• if you are going to have an operation (surgery) or be given anaesthetics. 
• if you are taking any of the following medicines used to treat high blood pressure: 

- an ACE-inhibitor (for example enalapril, lisinopril, ramipril), in particular if you have 
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diabetes-related kidney problems. 
- aliskiren 

 
Your doctor may check your kidney function, blood pressure, and the amount of electrolytes (e.g. 
potassium) in your blood at regular intervals. 
See also information under the heading “Do not take Sabervel’’. 
 
You must tell your doctor if you think you are (or might become) pregnant. Sabervel is not 
recommended in early pregnancy, and must not be taken if you are more than 3 months pregnant, as it 
may cause serious harm to your baby if used at that stage (see pregnancy section). 
 
Use in Children 
This medicine should not be used in children and adolescents (under 18 years) because the safety and 
efficacy have not yet been fully established. 
 
Other medicines and Sabervel 
Tell your doctor or pharmacist if you are taking , have recently taken or might take any other 
medicines. 
 
Your doctor may need to change your dose and/or to take other precautions: 
If you are taking an ACE-inhibitor or aliskiren (see also information under the headings “Do not take 
Sabervel” and “Warnings and precautions”). 
 
You may need to have blood checks if you take: 
• potassium supplements 
• salt substitutes containing potassium 
• potassium-sparing medicines (such as certain diuretics) 
• medicines containing lithium 
 
If you take certain painkillers, called non-steroidal anti-inflammatory drugs, the effect of irbesartan 
may be reduced. 
 
Taking Sabervel with food and drink 
Sabervel can be taken with or without food. 
 
Pregnancy and breast-feeding 
Pregnancy 
You must tell your doctor if you think you are (or might become) pregnant. Your doctor will normally 
advise you to stop taking Sabervel before you become pregnant or as soon as you know you are 
pregnant and will advise you to take another medicine instead of Sabervel. Sabervel is not 
recommended in early pregnancy, and must not be taken when more than 3 months pregnant, as it may 
cause serious harm to your baby if used after the third month of pregnancy. 
 
Breast-feeding 
Tell your doctor if you are breast-feeding or about to start breast-feeding. Sabervel is not 
recommended for mothers who are breast-feeding, and your doctor may choose another treatment for 
you if you wish to breast-feed, especially if your baby is newborn, or was born prematurely. 
 
Driving and using machines 
No studies on the effects on the ability to drive and use machines have been performed. Sabervel is 
unlikely to affect your ability to drive or use machines. However, occasionally dizziness or weariness 
may occur during treatment of high blood pressure. If you experience these, talk to your doctor before 
attempting to drive or use machines. 
 
Important information about some of the ingredients of Sabervel 
Sabervel contains lactose. If you have been told by your doctor that you have an intolerance to some 
sugars (e.g. lactose), contact your doctor before taking this medicine. 

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3. HOW TO TAKE SABERVEL 
 
Always take Sabervel exactly as your doctor has told you. You should check with your doctor or 
pharmacist if you are not sure. 
 
Method of administration 
Sabervel is for oral use . Swallow the tablets with a sufficient amount of fluid (e.g. one glass of water). 
You can take Sabervel with or without food. Try to take your daily dose at about the same time each 
day. It is important that you continue to take Sabervel until your doctor tells you otherwise. 
 
• Patients with high blood pressure 

The usual dose is 150 mg once a day. The dose may later be increased to 300 mg once daily 
depending on blood pressure response. 

 
• Patients with high blood pressure and type 2 diabetes with kidney disease 

In patients with high blood pressure and type 2 diabetes, 300 mg once daily is the preferred 
maintenance dose for the treatment of associated kidney disease. 

 
The doctor may advise a lower dose, especially when starting treatment in certain patients such as 
those on haemodialysis, or those over the age of 75 years . 
 
The maximal blood pressure lowering effect should be reached 4-6 weeks after beginning treatment. 
 
If you take more Sabervel than you should: 
If you accidentally take too many tablets, contact your doctor immediately. 
 
Children should not take Sabervel 
Sabervel should not be given to children under 18 years of age. If a child swallows some tablets, 
contact your doctor immediately. 
 
If you forget to take Sabervel: 
If you accidentally miss a daily dose, just take the next dose as normal. Do not take a double dose to 
make up for a forgotten dose. 
 
If you have any further questions on the use of this product, ask your doctor or pharmacist. 
 
 
4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, Sabervel can cause side effects, although not everybody gets them. Some of these 
effects may be serious and may require medical attention. 
 
As with similar medicines, rare cases of allergic skin reactions (rash, urticaria), as well as localised 
swelling of the face, lips and/or tongue have been reported in patients taking irbesartan. If you get any 
of these symptoms or get short of breath, stop taking Sabervel and contact your doctor 
immediately. 
 
The frequency of the side effects listed below is defined using the following convention:  
Very common: at least 1 in 10 patients or more 
Common: at least 1 in 100 and less than 1 in 10 patients 
Uncommon: at least 1 in 1000 and less than 1 in 100 patients 
Side effects reported in clinical studies for patients treated with  Irbesartan were: 
• Very common : if you suffer from high blood pressure and type 2 diabetes with kidney disease, 

blood tests may show an increased level of potassium. 
 

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• Common : dizziness, feeling sick/vomiting, fatigue and blood tests may show raised levels of an 
enzyme that measures the muscle and heart function (creatine kinase enzyme). In patients with 
high blood pressure and type 2 diabetes with kidney disease, dizziness when getting up from a 
lying or sitting position, low blood pressure when getting up from a lying or sitting position, 
pain in joints or muscles and decreased levels of a protein in the red blood cells (haemoglobin) 
were also reported. 

 
• Uncommon : heart rate increased, flushing, cough, diarrhoea, indigestion/heartburn, sexual 

dysfunction (problems with sexual performance), chest pain. 
 

Some side effects have been reported since marketing of Irbesartan Side effects where the frequency is 
not known are: feeling of spinning, headache, taste disturbance, ringing in the ears, muscle cramps, 
pain in joints and muscles, abnormal liver function, increased blood potassium levels, impaired kidney 
function, and inflammation of small blood vessels mainly affecting the skin (a condition known as 
leukocytoclastic vasculitis). 
Uncommon cases of jaundice (yellowing of the skin and/or whites of the eyes) have also been 
reported. 
 
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please 
tell your doctor or pharmacist. 
 
 
5. HOW TO STORE SABERVEL 
 
Keep out of the sight and reach of children. 
 
Do not use Sabervel after the expiry date which is stated on the carton and on the blister after EXP. 
The expiry date refers to the last day of that month. 
 
This medicinal product does not require any special storage conditions. 
 
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to 
dispose of medicines no longer required. These measures will help to protect the environment. 
 
 
6. FURTHER INFORMATION  
 
What Sabervel contains 
 
• The active substance is irbesartan. Each tablet of Sabervel 150 mg contains 150 mg irbesartan. 
• The other ingredients are:  

Tablet core: lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, silica 
colloidal anhydrous, hypromellose, magnesium stearate,  
Film-coating: hypromellose, titanium dioxide (E171), macrogol 400 

 
What Sabervel looks like and contents of the pack 
Sabervel 150 mg film-coated tablets are white, concave, round, film-coated tablets with 9 mm 
diameter. 
 
Sabervel 150mg film-coated tablets are supplied in blister packs of 28, 56, 90 or 98 film- coated 
tablets.  
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder: 
Pharmathen S.A,  
6 Dervenakion Str.,  

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15351 Pallini, Attiki, Greece 
 
Manufacturer: 
 
J. Uriach y Compañía, S.A. 
Av. Camí Reial, 51-57 
08184 – Palau-solità i Plegamans, Barcelona, Spain 
 
Pharmathen S.A,  
6 Dervenakion Str.,  
15351 Pallini, Attiki, Greece 
 
Pharmathen International S.A. 
Industrial Park Sapes,  
Rodopi Prefecture, Block No 5, Rodopi 69300, Greece 
 
For any information about this medicinal product, please contact the local representative of the 
Marketing Authorisation Holder. 
 
België/Belgique/Belgien 
Pharmathen S.A. 
Tél/Tel: +30 210 66 65 067 
 

Lietuva 
Portfarma ehf. 
Tel: +354 534 4030  
 

България  
Pharmathen S.A. 
Teл.: +30 210 66 65 067 
 

Luxembourg/Luxemburg 
Portfarma ehf. 
Tel: +354 534 4030 

Česká republika 
Pharmathen S.A. 
Tel: +30 210 66 65 067 
 

Magyarország  
Pharmathen S.A. 
Tel.: +30 210 66 65 067 
 

Danmark 
Portfarma ehf. 
Tlf: +354 534 4030 
 

Malta 
Pharmathen S.A. 
Tel: +30 210 66 65 067 
 

Deutschland 
Glenmark Arzneimittel GmbH 
Tel: +49 8142 44392 0 

Nederland 
Glenmark Generics B.V.   
Tel: 0031 20 5226030 
 

Eesti (Estonia) 
Portfarma ehf. 
Tel: +354 534 4030 
 

Norge 
Pharmathen S.A. 
Tlf: +30 210 66 65 067 
 

Ελλάδα 
Pharmathen Hellas S.A. 
Τηλ: +30 210 66 04 300 
 

Österreich  
Pharmathen S.A. 
Tel: +30 210 66 65 067 

España 
Pharmathen S.A. 
Tel: +30 210 66 65 067 
 

Polska 
Pharmathen S.A. 
Tel.: +30 210 66 65 067 

France 
Pharmathen S.A. 
Tél: +30 210 66 65 067 
 

Portugal 
Pharmathen S.A. 
Tel: +30 210 66 65 067 

Hrvatska 
Pharmathen S.A. 

România 
Pharmathen S.A. 

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Tel: +30 210 66 65 067 Tel: +30 210 66 65 067 
 
Ireland 
Aspire Pharma Limited 
Tel: +44(0)1730 234527 

 
Slovenija 
Pharmathen S.A. 
Tel: +30 210 66 65 067 

 
Ísland 
Portfarma ehf. 
Tel: +354 534 4030 

 
Slovenská republika  
Pharmathen S.A. 
Tel: +30 210 66 65 067 

 
Italia 
Pharmathen S.A. 
Tel: +30 210 66 65 067 

 
Suomi/Finland 
Pharmathen S.A. 
Puh/Tel: +30 210 66 65 067 

 
Κύπρος 
C.V. MEDILINE LTD  
Τηλ: +357 25761699 

 
Sverige  
Pharmathen S.A. 
Tel: +30 210 66 65 067 
 

Latvija  
Portfarma ehf. 
Tel: +354 534 4030 
 

United Kingdom 
Aspire Pharma Limited 
Tel: +44(0)1730 234527 

 
This leaflet was last approved  in 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 
 

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


PACKAGE LEAFLET: INFORMATION FOR THE USER  
 

Sabervel 300 mg film-coated tablets 
irbesartan 

 
Read all of this leaflet carefully before you start taking this medicine . 
• 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. Do not pass it on to others. It may harm them, even 

if their symptoms are the same as yours. 
• If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 
 
In this leaflet: 
1. What Sabervel is and what it is used for 
2. Before you take Sabervel 
3. How to take Sabervel 
4. Possible side effects 
5. How to store Sabervel 
6. Further information 
 
 
1. WHAT SABERVEL IS AND WHAT IT IS USED FOR 
 
Sabervel belongs to a group of medicines known as angiotensin-II receptor antagonists. Angiotensin-II 
is a substance produced in the body which binds to receptors in blood vessels causing them to tighten. 
This results in an increase in blood pressure. Sabervel prevents the binding of angiotensin-II to these 
receptors, causing the blood vessels to relax and the blood pressure to lower. Sabervel slows the 
decrease of kidney function in patients with high blood pressure and type 2 diabetes. 
 
Sabervel is used in adult patients 
• to treat high blood pressure (essential hypertension) 
• to protect the kidney in patients with high blood pressure, type 2 diabetes and laboratory 

evidence of impaired kidney function. 
 
 
2. BEFORE YOU TAKE SABERVEL  
 
Do not take Sabervel 
• if you are allergic (hypersensitive) to irbesartan or any other ingredients of Sabervel 
• if you are more than 3 months pregnant. (It is also better to avoid Sabervel in early pregnancy 

– see pregnancy section) 
• if you have diabetes or impaired kidney function and you are treated with a blood pressure 

lowering medicine containing aliskiren. 
 
Warning and precautions  
Tell your doctor if any of the following apply to you: 
• if you get excessive vomiting or diarrhoea 
• if you suffer from kidney problems  
• if you suffer from heart problems  
• if you receive Sabervel for diabetic kidney disease. In this case your doctor may perform 

regular blood tests, especially for measuring blood potassium levels in case of poor kidney 
function 

• if you are going to have an operation (surgery) or be given anaesthetics. 
• if you are taking any of the following medicines used to treat high blood pressure: 

- an ACE-inhibitor (for example enalapril, lisinopril, ramipril), in particular if you have 
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diabetes-related kidney problems. 
- aliskiren 

 
Your doctor may check your kidney function, blood pressure, and the amount of electrolytes (e.g. 
potassium) in your blood at regular intervals. 
See also information under the heading “Do not take Sabervel”. 
 
You must tell your doctor if you think you are (or might become) pregnant. Sabervel is not 
recommended in early pregnancy, and must not be taken if you are more than 3 months pregnant, as it 
may cause serious harm to your baby if used at that stage (see pregnancy section). 
 
Use in Children 
This medicine should not be used in children and adolescents (under 18 years) because the safety and 
efficacy have not yet been fully established. 
 
Other medicines and Sabervel 
Tell your doctor or pharmacist if you are taking , have recently taken or might take any other 
medicines. 
 
Your doctor may need to change your dose and/or to take other precautions: 
 
If you are taking an ACE-inhibitor or aliskiren (see also information under the headings “Do not take 
Sabervel” and “Warnings and precautions”). 
 
You may need to have blood checks if you take: 
• potassium supplements 
• salt substitutes containing potassium 
• potassium-sparing medicines (such as certain diuretics) 
• medicines containing lithium 
 
If you take certain painkillers, called non-steroidal anti-inflammatory drugs, the effect of irbesartan 
may be reduced. 
 
Taking Sabervel with food and drink 
Sabervel can be taken with or without food. 
 
Pregnancy and breast-feeding 
Pregnancy 
You must tell your doctor if you think you are (or might become) pregnant. Your doctor will normally 
advise you to stop taking Sabervel before you become pregnant or as soon as you know you are 
pregnant and will advise you to take another medicine instead of Sabervel. Sabervel is not 
recommended in early pregnancy, and must not be taken when more than 3 months pregnant, as it may 
cause serious harm to your baby if used after the third month of pregnancy. 
 
Breast-feeding 
Tell your doctor if you are breast-feeding or about to start breast-feeding. Sabervel is not 
recommended for mothers who are breast-feeding, and your doctor may choose another treatment for 
you if you wish to breast-feed, especially if your baby is newborn, or was born prematurely. 
 
Driving and using machines 
No studies on the effects on the ability to drive and use machines have been performed. Sabervel is 
unlikely to affect your ability to drive or use machines. However, occasionally dizziness or weariness 
may occur during treatment of high blood pressure. If you experience these, talk to your doctor before 
attempting to drive or use machines. 
 
Important information about some of the ingredients of Sabervel 
Sabervel contains lactose. If you have been told by your doctor that you have an intolerance to some 

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sugars (e.g. lactose), contact your doctor before taking this medicine. 
 
 
3. HOW TO TAKE SABERVEL 
 
Always take Sabervel exactly as your doctor has told you. You should check with your doctor or 
pharmacist if you are not sure. 
 
Method of administration 
Sabervel is for oral use . Swallow the tablets with a sufficient amount of fluid (e.g. one glass of water). 
You can take Sabervel with or without food. Try to take your daily dose at about the same time each 
day. It is important that you continue to take Sabervel until your doctor tells you otherwise. 
 
• Patients with high blood pressure 

The usual dose is 150 mg once a day. The dose may later be increased to 300 mg once daily 
depending on blood pressure response. 

 
• Patients with high blood pressure and type 2 diabetes with kidney disease 

In patients with high blood pressure and type 2 diabetes, 300 mg once daily is the preferred 
maintenance dose for the treatment of associated kidney disease. 

 
The doctor may advise a lower dose, especially when starting treatment in certain patients such as 
those on haemodialysis, or those over the age of 75 years . 
 
The maximal blood pressure lowering effect should be reached 4-6 weeks after beginning treatment. 
 
If you take more Sabervel than you should: 
If you accidentally take too many tablets, contact your doctor immediately. 
 
Children should not take Sabervel 
Sabervel should not be given to children under 18 years of age. If a child swallows some tablets, 
contact your doctor immediately. 
 
If you forget to take Sabervel: 
If you accidentally miss a daily dose, just take the next dose as normal. Do not take a double dose to 
make up for a forgotten dose. 
 
If you have any further questions on the use of this product, ask your doctor or pharmacist. 
 
 
4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, Sabervel can cause side effects, although not everybody gets them. Some of these 
effects may be serious and may require medical attention. 
 
As with similar medicines, rare cases of allergic skin reactions (rash, urticaria), as well as localised 
swelling of the face, lips and/or tongue have been reported in patients taking irbesartan. If you get any 
of these symptoms or get short of breath, stop taking Sabervel and contact your doctor 
immediately. 
 
The frequency of the side effects listed below is defined using the following convention:  
Very common: at least 1 in 10 patients or more 
Common: at least 1 in 100 and less than 1 in 10 patients 
Uncommon: at least 1 in 1000 and less than 1 in 100 patients 
 

Side effects reported in clinical studies for patients treated with Irbesartan were: 
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• Very common : if you suffer from high blood pressure and type 2 diabetes with kidney disease, 
blood tests may show an increased level of potassium. 

 
• Common : dizziness, feeling sick/vomiting, fatigue and blood tests may show raised levels of an 

enzyme that measures the muscle and heart function (creatine kinase enzyme). In patients with 
high blood pressure and type 2 diabetes with kidney disease, dizziness when getting up from a 
lying or sitting position, low blood pressure when getting up from a lying or sitting position, 
pain in joints or muscles and decreased levels of a protein in the red blood cells (haemoglobin) 
were also reported. 

 
• Uncommon : heart rate increased, flushing, cough, diarrhoea, indigestion/heartburn, sexual 

dysfunction (problems with sexual performance), chest pain. 
 

Some side effects have been reported since marketing of Irbesartan Side effects where the frequency is 
not known are: feeling of spinning, headache, taste disturbance, ringing in the ears, muscle cramps, 
pain in joints and muscles, abnormal liver function, increased blood potassium levels, impaired kidney 
function, and inflammation of small blood vessels mainly affecting the skin (a condition known as 
leukocytoclastic vasculitis). 
Uncommon cases of jaundice (yellowing of the skin and/or whites of the eyes) have also been 
reported. 
 
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please 
tell your doctor or pharmacist. 
 
 
5. HOW TO STORE SABERVEL 
 
Keep  out of the sight and reach of children. 
 
Do not use Sabervel after the expiry date which is stated on the carton and on the blister after EXP. 
The expiry date refers to the last day of that month. 
 
This medicinal product does not require any special storage conditions. 
 
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to 
dispose of medicines no longer required. These measures will help to protect the environment. 
 
 
6. FURTHER INFORMATION  
 
What Sabervel contains 
 
• The active substance is irbesartan. Each tablet of Sabervel 300 mg contains 300 mg irbesartan. 
• The other ingredients are:  

Tablet core: lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, silica 
colloidal anhydrous, hypromellose, magnesium stearate,  
Film-coating: hypromellose, titanium dioxide (E171), macrogol 400 

 
What Sabervel looks like and contents of the pack 
Sabervel 300 mg film-coated tablets are white, concave, round, film-coated tablets with 11 mm 
diameter.  
 
Sabervel 300mg film-coated tablets are supplied in blister packs of 28, 56, 90 or 98 film- coated 
tablets.  
 
Not all pack sizes may be marketed. 
 

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Marketing Authorisation Holder: 
Pharmathen S.A,  
6 Dervenakion Str.,  
15351 Pallini, Attiki, Greece 
 
Manufacturer: 
 
J. Uriach y Compañía, S.A. 
Av. Camí Reial, 51-57 
08184 – Palau-solità i Plegamans, Barcelona, Spain 
 
Pharmathen S.A,  
6 Dervenakion Str.,  
15351 Pallini, Attiki, Greece 
 
Pharmathen International S.A. 
Industrial Park Sapes,  
Rodopi Prefecture, Block No 5, Rodopi 69300, Greece 
 
For any information about this medicinal product, please contact the local representative of the 
Marketing Authorisation Holder. 
 
België/Belgique/Belgien 
Pharmathen S.A. 
Tél/Tel: +30 210 66 65 067 
 

Lietuva 
Portfarma ehf. 
Tel: +354 534 4030  
 

България  
Pharmathen S.A. 
Teл.: +30 210 66 65 067 
 

Luxembourg/Luxemburg 
Portfarma ehf. 
Tel: +354 534 4030 

Česká republika 
Pharmathen S.A. 
Tel: +30 210 66 65 067 
 

Magyarország  
Pharmathen S.A. 
Tel.: +30 210 66 65 067 
 

Danmark 
Portfarma ehf. 
Tlf: +354 534 4030 
 

Malta 
Pharmathen S.A. 
Tel: +30 210 66 65 067 
 

Deutschland 
Glenmark Arzneimittel GmbH 
Tel: +49 8142 44392 0 

Nederland 
Glenmark Generics B.V.   
Tel: 0031 20 5226030 
 

Eesti (Estonia) 
Portfarma ehf. 
Tel: +354 534 4030 
 

Norge 
Pharmathen S.A. 
Tlf: +30 210 66 65 067 
 

Ελλάδα 
Pharmathen Hellas S.A. 
Τηλ: +30 210 66 04 300 
 

Österreich  
Pharmathen S.A. 
Tel: +30 210 66 65 067 

España 
Pharmathen S.A. 
Tel: +30 210 66 65 067 
 

Polska 
Pharmathen S.A. 
Tel.: +30 210 66 65 067 

France 
Pharmathen S.A. 
Tél: +30 210 66 65 067 

Portugal 
Pharmathen S.A. 
Tel: +30 210 66 65 067 

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Hrvatska 
Pharmathen S.A. 
Tel: +30 210 66 65 067 

România 
Pharmathen S.A. 
Tel: +30 210 66 65 067 

 
Ireland 
Aspire Pharma Limited 
Tel: +44(0)1730 234527 

 
Slovenija 
Pharmathen S.A. 
Tel: +30 210 66 65 067 

 
Ísland 
Portfarma ehf. 
Tel: +354 534 4030 

 
Slovenská republika  
Pharmathen S.A. 
Tel: +30 210 66 65 067 

 
Italia 
Pharmathen S.A. 
Tel: +30 210 66 65 067 

 
Suomi/Finland 
Pharmathen S.A. 
Puh/Tel: +30 210 66 65 067 

 
Κύπρος 
C.V. MEDILINE LTD  
Τηλ: +357 25761699 
 

 
Sverige  
Pharmathen S.A. 
Tel: +30 210 66 65 067 
 

Latvija  
Portfarma ehf. 
Tel: +354 534 4030 
 

United Kingdom 
Aspire Pharma Limited 
Tel: +44(0)1730 234527 

 
This leaflet was last approved  in 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/ 

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	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS 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
{'Title': '1. what sabervel is and what it is used for', 'Section_Content': 'sabervel belongs to a group of medicines known as angiotensin-ii receptor antagonists. angiotensin-ii is a substance produced in the body which binds to receptors in blood vessels causing them to tighten. this results in an increase in blood pressure. sabervel prevents the binding of angiotensin-ii to these receptors, causing the blood vessels to relax and the blood pressure to lower. sabervel slows the decrease of kidney function in patients with high blood pressure and type 2 diabetes. sabervel is used in adult patients to treat high blood pressure (essential hypertension) to protect the kidney in patients with high blood pressure, type 2 diabetes and laboratory evidence of impaired kidney function.', 'Entity_Recognition': [{'Text': 'sabervel', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': 'a group of medicines', 'Type': 'TREATMENT', 'BeginOffset': 20, 'EndOffset': 40}, {'Text': 'angiotensin', 'Type': 'TREATMENT', 'BeginOffset': 50, 'EndOffset': 61}, {'Text': 'ii receptor antagonists', 'Type': 'TREATMENT', 'BeginOffset': 62, 'EndOffset': 85}, {'Text': 'angiotensin', 'Type': 'TREATMENT', 'BeginOffset': 87, 'EndOffset': 98}, {'Text': 'blood pressure', 'Type': 'TEST', 'BeginOffset': 236, 'EndOffset': 250}, {'Text': 'the blood vessels', 'Type': 'PROBLEM', 'BeginOffset': 328, 'EndOffset': 345}, {'Text': 'the blood pressure', 'Type': 'TEST', 'BeginOffset': 359, 'EndOffset': 377}, {'Text': 'the decrease of kidney function', 'Type': 'PROBLEM', 'BeginOffset': 403, 'EndOffset': 434}, {'Id': 5, 'BeginOffset': 452, 'EndOffset': 471, 'Score': 0.8131152987480164, 'Text': 'high blood pressure', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'DIAGNOSIS', 'Score': 0.5999765992164612}]}, {'Id': 6, 'BeginOffset': 476, 'EndOffset': 491, 'Score': 0.4475242793560028, 'Text': 'type 2 diabetes', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'DIAGNOSIS', 'Score': 0.9344425797462463}]}, {'Text': '2', 'Type': 'NUMBER', 'BeginOffset': 481, 'EndOffset': 482}, {'Id': 7, 'BeginOffset': 537, 'EndOffset': 556, 'Score': 0.9367955923080444, 'Text': 'high blood pressure', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'DIAGNOSIS', 'Score': 0.8974476456642151}]}, {'Text': 'essential hypertension', 'Type': 'PROBLEM', 'BeginOffset': 558, 'EndOffset': 580}, {'Id': 2, 'BeginOffset': 597, 'EndOffset': 603, 'Score': 0.9663722515106201, 'Text': 'kidney', 'Category': 'ANATOMY', 'Type': 'SYSTEM_ORGAN_SITE', 'Traits': []}, {'Id': 9, 'BeginOffset': 621, 'EndOffset': 640, 'Score': 0.843540608882904, 'Text': 'high blood pressure', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'DIAGNOSIS', 'Score': 0.7835363149642944}]}, {'Id': 10, 'BeginOffset': 642, 'EndOffset': 657, 'Score': 0.6343913078308105, 'Text': 'type 2 diabetes', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'DIAGNOSIS', 'Score': 0.9182752370834351}]}, {'Text': '2', 'Type': 'NUMBER', 'BeginOffset': 647, 'EndOffset': 648}, {'Id': 11, 'BeginOffset': 685, 'EndOffset': 709, 'Score': 0.873258113861084, 'Text': 'impaired kidney function', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SIGN', 'Score': 0.4983729422092438}, {'Name': 'DIAGNOSIS', 'Score': 0.49219319224357605}]}, {'Id': 3, 'BeginOffset': 694, 'EndOffset': 700, 'Score': 0.9793952107429504, 'Text': 'kidney', 'Category': 'ANATOMY', 'Type': 'SYSTEM_ORGAN_SITE', 'Traits': []}]}
{'Title': '2. before you take sabervel', 'Section_Content': 'do not take sabervel if you are allergic (hypersensitive) to irbesartan or any other ingredients of sabervel if you are more than 3 months pregnant. (it is also better to avoid sabervel in early pregnancy see pregnancy section) if you have diabetes or impaired kidney function and you are treated with a blood pressure lowering medicine containing aliskiren. warnings and precautions tell your doctor if any of the following apply to you: if you get excessive vomiting or diarrhoea if you suffer from kidney problems if you suffer from heart problems if you receive sabervel for diabetic kidney disease. in this case your doctor may perform regular blood tests, especially for measuring blood potassium levels in case of poor kidney function if you are going to have an operation (surgery) or be given anaesthetics. if you are taking any of the following medicines used to treat high blood pressure: - an ace-inhibitor (for example enalapril, lisinopril, ramipril), in particular if you have diabetes-related kidney problems. - aliskiren your doctor may check your kidney function, blood pressure, and the amount of electrolytes (e.g. potassium) in your blood at regular intervals. see also information under the heading "do not take sabervel". you must tell your doctor if you think you are (or might become) pregnant. sabervel is not recommended in early pregnancy, and must not be taken if you are more than 3 months pregnant, as it may cause serious harm to your baby if used at that stage (see pregnancy section). use in children this medicine should not be used in children and adolescents (under 18 years) because the safety and efficacy have not yet been fully established. other medicines and sabervel tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. your doctor may need to change your dose and/or to take other precautions: if you are taking an ace-inhibitor or aliskiren (see also information under the headings "do not take sabervel" and "warnings and precautions"). you may need to have blood checks if you take: potassium supplements salt substitutes containing potassium potassium-sparing medicines (such as certain diuretics) medicines containing lithium if you take certain painkillers, called non-steroidal anti-inflammatory drugs, the effect of irbesartan may be reduced. taking sabervel with food and drink sabervel can be taken with or without food. pregnancy and breast-feeding pregnancy you must tell your doctor if you think you are (or might become) pregnant. your doctor will normally advise you to stop taking sabervel before you become pregnant or as soon as you know you are pregnant and will advise you to take another medicine instead of sabervel. sabervel is not recommended in early pregnancy, and must not be taken when more than 3 months pregnant, as it may cause serious harm to your baby if used after the third month of pregnancy. breast-feeding tell your doctor if you are breast-feeding or about to start breast-feeding. sabervel is not recommended for mothers who are breast-feeding, and your doctor may choose another treatment for you if you wish to breast-feed, especially if your baby is newborn, or was born prematurely. driving and using machines no studies on the effects on the ability to drive and use machines have been performed. sabervel is unlikely to affect your ability to drive or use machines. however, occasionally dizziness or weariness may occur during treatment of high blood pressure. if you experience these, talk to your doctor before attempting to drive or use machines. important information about some of the ingredients of sabervel sabervel contains lactose. if you have been told by your doctor that you have an intolerance to some sugars (e.g. lactose), contact your doctor before taking this medicine.', 'Entity_Recognition': [{'Text': 'sabervel', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': 'allergic', 'Type': 'PROBLEM', 'BeginOffset': 32, 'EndOffset': 40}, {'Id': 17, 'BeginOffset': 42, 'EndOffset': 56, 'Score': 0.7493985295295715, 'Text': 'hypersensitive', 'Category': 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{'Title': '3. how to take sabervel', 'Section_Content': 'always take sabervel exactly as your doctor has told you. you should check with your doctor or pharmacist if you are not sure. method of administration sabervel is for oral use . swallow the tablets with a sufficient amount of fluid (e.g. one glass of water). you can take sabervel with or without food. try to take your daily dose at about the same time each day. it is important that you continue to take sabervel until your doctor tells you otherwise. patients with high blood pressure the usual dose is 150 mg once a day. the dose may later be increased to 300 mg once daily depending on blood pressure response. patients with high blood pressure and type 2 diabetes with kidney disease in patients with high blood pressure and type 2 diabetes, 300 mg once daily is the preferred maintenance dose for the treatment of associated kidney disease. the doctor may advise a lower dose, especially when starting treatment in certain patients such as those on haemodialysis, or those over the age of 75 years . the maximal blood pressure lowering effect should be reached 4-6 weeks after beginning treatment. if you take more sabervel than you should: if you accidentally take too many tablets, contact your doctor immediately. children should not take sabervel sabervel should not be given to children under 18 years of age. if a child swallows some tablets, contact your doctor immediately. if you forget to take sabervel: if you accidentally miss a daily dose, just take the next dose as normal. do not take a double dose to make up for a forgotten dose. if you have any further questions on the use of this product, ask your doctor or pharmacist.', 'Entity_Recognition': [{'Text': 'sabervel', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': 'method of administration sabervel', 'Type': 'TREATMENT', 'BeginOffset': 127, 'EndOffset': 160}, {'Text': 'swallow', 'Type': 'TREATMENT', 'BeginOffset': 179, 'EndOffset': 186}, {'Text': 'high blood pressure', 'Type': 'TREATMENT', 'BeginOffset': 469, 'EndOffset': 488}, {'Text': '150', 'Type': 'NUMBER', 'BeginOffset': 507, 'EndOffset': 510}, {'Text': '300', 'Type': 'NUMBER', 'BeginOffset': 561, 'EndOffset': 564}, {'Text': 'blood pressure response', 'Type': 'TEST', 'BeginOffset': 592, 'EndOffset': 615}, {'Id': 8, 'BeginOffset': 631, 'EndOffset': 650, 'Score': 0.7963448762893677, 'Text': 'high blood pressure', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'DIAGNOSIS', 'Score': 0.7422379851341248}]}, {'Id': 9, 'BeginOffset': 655, 'EndOffset': 670, 'Score': 0.5227233171463013, 'Text': 'type 2 diabetes', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'DIAGNOSIS', 'Score': 0.9489775896072388}]}, {'Text': '2', 'Type': 'NUMBER', 'BeginOffset': 660, 'EndOffset': 661}, {'Id': 10, 'BeginOffset': 676, 'EndOffset': 690, 'Score': 0.942183792591095, 'Text': 'kidney disease', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'DIAGNOSIS', 'Score': 0.9702832102775574}]}, {'Id': 11, 'BeginOffset': 708, 'EndOffset': 727, 'Score': 0.772372305393219, 'Text': 'high blood pressure', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'DIAGNOSIS', 'Score': 0.7153275609016418}]}, {'Text': 'type 2 diabetes', 'Type': 'PROBLEM', 'BeginOffset': 732, 'EndOffset': 747}, {'Text': '2', 'Type': 'NUMBER', 'BeginOffset': 737, 'EndOffset': 738}, {'Text': '300', 'Type': 'NUMBER', 'BeginOffset': 749, 'EndOffset': 752}, {'Text': 'associated kidney disease', 'Type': 'PROBLEM', 'BeginOffset': 822, 'EndOffset': 847}, {'Text': 'treatment', 'Type': 'TREATMENT', 'BeginOffset': 910, 'EndOffset': 919}, {'Id': 15, 'BeginOffset': 957, 'EndOffset': 970, 'Score': 0.6086317896842957, 'Text': 'haemodialysis', 'Category': 'TEST_TREATMENT_PROCEDURE', 'Type': 'TREATMENT_NAME', 'Traits': []}, {'Id': 14, 'BeginOffset': 997, 'EndOffset': 999, 'Score': 0.8379294276237488, 'Text': '75', 'Category': 'PROTECTED_HEALTH_INFORMATION', 'Type': 'AGE', 'Traits': []}, {'Text': 'the maximal blood pressure', 'Type': 'TEST', 'BeginOffset': 1008, 'EndOffset': 1034}, {'Text': '18', 'Type': 'NUMBER', 'BeginOffset': 1306, 'EndOffset': 1308}, {'Text': 'a double dose', 'Type': 'TREATMENT', 'BeginOffset': 1508, 'EndOffset': 1521}]}
{'Title': '4. possible side effects', 'Section_Content': 'like all medicines, sabervel can cause side effects, although not everybody gets them. some of these effects may be serious and may require medical attention. as with similar medicines, rare cases of allergic skin reactions (rash, urticaria), as well as localised swelling of the face, lips and/or tongue have been reported in patients taking irbesartan. if you get any of these symptoms or get short of breath, stop taking sabervel and contact your doctor immediately. the frequency of the side effects listed below is defined using the following convention: very common: at least 1 in 10 patients or more common: at least 1 in 100 and less than 1 in 10 patients uncommon: at least 1 in 1000 and less than 1 in 100 patientsside effects reported in clinical studies for patients treated with irbesartan were: very common : if you suffer from high blood pressure and type 2 diabetes with kidney disease, blood tests may show an increased level of potassium. common : dizziness, feeling sick/vomiting, fatigue and blood tests may show raised levels of an enzyme that measures the muscle and heart function (creatine kinase enzyme). in patients with high blood pressure and type 2 diabetes with kidney disease, dizziness when getting up from a lying or sitting position, low blood pressure when getting up from a lying or sitting position, pain in joints or muscles and decreased levels of a protein in the red blood cells (haemoglobin) were also reported. uncommon : heart rate increased, flushing, cough, diarrhoea, indigestion/heartburn, sexual dysfunction (problems with sexual performance), chest pain. some side effects have been reported since marketing of irbesartan side effects where the frequency is not known are: feeling of spinning, headache, taste disturbance, ringing in the ears, muscle cramps, pain in joints and muscles, abnormal liver function, increased blood potassium levels, impaired kidney function, and inflammation of small blood vessels mainly affecting the skin (a condition known as leukocytoclastic vasculitis). uncommon cases of jaundice (yellowing of the skin and/or whites of the eyes) have also been reported. if any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.', 'Entity_Recognition': [{'Text': 'sabervel', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': 'all medicines', 'Type': 'TREATMENT', 'BeginOffset': 5, 'EndOffset': 18}, {'Text': 'sabervel', 'Type': 'TREATMENT', 'BeginOffset': 20, 'EndOffset': 28}, {'Id': 23, 'BeginOffset': 39, 'EndOffset': 51, 'Score': 0.9583647847175598, 'Text': 'side effects', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.6198253035545349}]}, {'Text': 'similar medicines', 'Type': 'TREATMENT', 'BeginOffset': 167, 'EndOffset': 184}, {'Id': 24, 'BeginOffset': 200, 'EndOffset': 223, 'Score': 0.7788938283920288, 'Text': 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{'Title': '5. how to store sabervel', 'Section_Content': 'keep out of the sight and reach of children. do not use sabervel after the expiry date which is stated on the carton and on the blister after exp. the expiry date refers to the last day of that month. this medicinal product does not require any special storage conditions. medicines should not be disposed of via wastewater or household waste. ask your pharmacist how to dispose of medicines no longer required. these measures will help to protect the environment.', 'Entity_Recognition': [{'Text': 'sabervel', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': 'sabervel', 'Type': 'TREATMENT', 'BeginOffset': 56, 'EndOffset': 64}, {'Text': 'medicines', 'Type': 'TREATMENT', 'BeginOffset': 273, 'EndOffset': 282}, {'Text': 'medicines', 'Type': 'TREATMENT', 'BeginOffset': 382, 'EndOffset': 391}, {'Text': 'these measures', 'Type': 'TREATMENT', 'BeginOffset': 412, 'EndOffset': 426}]}
{'Title': '6. further information', 'Section_Content': 'what sabervel contains the active substance is irbesartan. each tablet of sabervel 75 mg contains 75 mg irbesartan. the other ingredients are: tablet core: lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, silica colloidal anhydrous, hypromellose, magnesium stearate, film-coating: hypromellose, titanium dioxide (e171), macrogol 400 what sabervel looks like and contents of the pack sabervel 75 mg film-coated tablets are white, concave, round, film-coated tablets with 7 mm diameter. sabervel 75mg film-coated tablets are supplied in blister packs of 28, 56, 90 or 98 film- coated tablets. not all pack sizes may be marketed.', 'Entity_Recognition': [{'Text': 'sabervel', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Id': 0, 'BeginOffset': 47, 'EndOffset': 57, 'Score': 0.9920601844787598, 'Text': 'irbesartan', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': [], 'Attributes': [{'Type': 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