Irbesartan BMS

1

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Irbesartan BMS 75 mg tablets. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each tablet contains 75 mg of irbesartan. 
 
Excipient: 15.37 mg of lactose monohydrate per tablet. 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Tablet. 
White to off-white, biconvex, and oval-shaped with a heart debossed on one side and the number 2771 
engraved on the other side. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Treatment of essential hypertension. 
Treatment of renal disease in patients with hypertension and type 2 diabetes mellitus as part of an 
antihypertensive medicinal product regimen (see section 5.1). 
 
4.2 Posology and method of administration 
 
The usual recommended initial and maintenance dose is 150 mg once daily, with or without food. 
Irbesartan BMS 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 Irbesartan BMS can be 
increased to 300 mg, or other antihypertensive agents can be added. In particular, the addition of a 
diuretic such as hydrochlorothiazide has been shown to have an additive effect with Irbesartan BMS 
(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 Irbesartan BMS 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 section 5.1). 
 
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 
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. 
 

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Paediatric patients: irbesartan is not recommended for use in children and adolescents due to 
insufficient data on safety and efficacy (see sections 4.8, 5.1 and 5.2). 
 
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). 
 
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 Irbesartan 
BMS. 
 
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 Irbesartan BMS, a similar effect should be anticipated with angiotensin-II 
receptor antagonists. 
 
Renal impairment and kidney transplantation: when Irbesartan BMS 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 Irbesartan BMS 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). 
 
Hyperkalaemia: as with other medicinal products that affect the renin-angiotensin-aldosterone system, 
hyperkalaemia may occur during the treatment with Irbesartan BMS, 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). 
 
Lithium: the combination of lithium and Irbesartan BMS 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 Irbesartan BMS 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). 

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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 patients: 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 BMS 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 Irbesartan BMS (see section 4.4). 
 
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 
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. 
 

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4.6 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). 
 
Lactation: 
 
Because no information is available regarding the use of Irbesartan BMS during breast-feeding, 
Irbesartan BMS is not recommended and alternative treatments with better established safety profiles 
during breast-feeding are preferable, especially while nursing a newborn or preterm infant. 
 
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: 

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very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, 
< 1/1,000); very rare (< 1/10,000). Within each frequency grouping, undesirable effects are presented 
in order of decreasing seriousness. 
 
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. 

 
Cardiac disorders: 
Uncommon: tachycardia 
 
Nervous system disorders: 
Common: dizziness, orthostatic dizziness* 
 
Respiratory, thoracic and mediastinal disorders: 
Uncommon: cough 
 
Gastrointestinal disorders: 
Common: nausea/vomiting 
Uncommon: diarrhoea, dyspepsia/heartburn 
 
Musculoskeletal and connective tissue disorders: 
Common: musculoskeletal pain* 
 
Vascular disorders: 
Common: orthostatic hypotension* 
Uncommon: flushing 
 
General disorders and administration site conditions: 
Common: fatigue 
Uncommon: chest pain 
 
Reproductive system and breast disorders: 
Uncommon: sexual dysfunction 
 
The following additional adverse reactions have been reported during post–marketing 
experience; they are derived from spontaneous reports and therefore, the frequency of these 
adverse reactions is not known: 
 
Nervous system disorders: 
Headache 
 
Ear and labyrinth disorders: 
Tinnitus  
 

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Gastrointestinal disorders: 
Dysgeusia 
 
Renal and urinary disorders: 
Impaired renal function including cases of renal failure in patients at risk (see section 4.4) 
 
Skin and subcutaneous tissue disorders: 
Leukocytoclastic vasculitis 
 
Musculoskeletal and connective tissue disorders: 
Arthralgia, myalgia (in some cases associated with increased plasma creatine kinase levels), muscle 
cramps 
 
Metabolism and nutrition disorders: 
Hyperkalaemia 
 
Immune system disorders: 
Hypersensitivity reactions such as angioedema, rash, urticaria 
 
Hepato-biliary disorders: 
Hepatitis, abnormal liver function 
 
Paediatric patients: in a randomised trial of 318 hypertensive children and adolescents aged 6 to 
16 years, the following related adverse events 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. 
 
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 
Irbesartan BMS. 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. 
 

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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 BMS 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 BMS 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. 
 
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 
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 BMS, 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 BMS 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 BMS, 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 

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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 BMS 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 
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 BMS 300 mg group (34%) than in the placebo group (21%). 
 
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). 

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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. 
 
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. 
 
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 
 
Microcrystalline cellulose 
Croscarmellose sodium 
Lactose monohydrate 
Magnesium stearate 
Colloidal hydrated silica 
Pregelatinised maize starch 
Poloxamer 188 
 

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6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years. 
 
6.4 Special precautions for storage 
 
Do not store above 30°C. 
 
6.5 Nature and contents of container 
 
Cartons of 14 tablets: 1 blister card of 14 tablets in PVC/PVDC/Aluminium blisters. 
Cartons of 28 tablets: 2 blister cards of 14 tablets in PVC/PVDC/Aluminium blisters. 
Cartons of 56 tablets: 4 blister cards of 14 tablets in PVC/PVDC/Aluminium blisters. 
Cartons of 98 tablets: 7 blister cards of 14 tablets in PVC/PVDC/Aluminium blisters. 
Cartons of 56 x 1 tablet; 7 blister cards of 8 x 1 tablet each in PVC/PVDC/Aluminium perforated unit 
dose 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 
 
BRISTOL-MYERS SQUIBB PHARMA EEIG 
Uxbridge Business Park 
Sanderson Road 
Uxbridge UB8 1DH - United Kingdom 
 
 
8. MARKETING AUTHORISATION NUMBERS 
 
EU/1/06/375/001-005 
 
 
9. DATE OF FIRST AUTHORISATION / RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 19 January 2007 
Date of latest renewal: 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this product is available on the website of the European Medicines Agency 
(EMEA) http://www.emea.europa.eu/ 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Irbesartan BMS 150 mg tablets. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each tablet contains 150 mg of irbesartan. 
 
Excipient: 30.75 mg of lactose monohydrate per tablet. 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Tablet. 
White to off-white, biconvex, and oval-shaped with a heart debossed on one side and the number 2772 
engraved on the other side. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Treatment of essential hypertension. 
Treatment of renal disease in patients with hypertension and type 2 diabetes mellitus as part of an 
antihypertensive medicinal product regimen (see section 5.1). 
 
4.2 Posology and method of administration 
 
The usual recommended initial and maintenance dose is 150 mg once daily, with or without food. 
Irbesartan BMS 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 Irbesartan BMS can be 
increased to 300 mg, or other antihypertensive agents can be added. In particular, the addition of a 
diuretic such as hydrochlorothiazide has been shown to have an additive effect with Irbesartan BMS 
(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 Irbesartan BMS 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 section 5.1). 
 
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 
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. 
 

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Paediatric patients: irbesartan is not recommended for use in children and adolescents due to 
insufficient data on safety and efficacy (see sections 4.8, 5.1 and 5.2). 
 
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). 
 
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 Irbesartan 
BMS. 
 
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 Irbesartan BMS, a similar effect should be anticipated with angiotensin-II 
receptor antagonists. 
 
Renal impairment and kidney transplantation: when Irbesartan BMS 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 Irbesartan BMS 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). 
 
Hyperkalaemia: as with other medicinal products that affect the renin-angiotensin-aldosterone system, 
hyperkalaemia may occur during the treatment with Irbesartan BMS, 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). 
 
Lithium: the combination of lithium and Irbesartan BMS 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 Irbesartan BMS 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). 

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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 patients: 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 BMS 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 Irbesartan BMS (see section 4.4). 
 
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 
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. 
 

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4.6 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). 
 
Lactation: 
 
Because no information is available regarding the use of Irbesartan BMS during breast-feeding, 
Irbesartan BMS is not recommended and alternative treatments with better established safety profiles 
during breast-feeding are preferable, especially while nursing a newborn or preterm infant. 
 
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: 

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very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, 
< 1/1,000); very rare (< 1/10,000). Within each frequency grouping, undesirable effects are presented 
in order of decreasing seriousness. 
 
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. 

 
Cardiac disorders: 
Uncommon: tachycardia 
 
Nervous system disorders: 
Common: dizziness, orthostatic dizziness* 
 
Respiratory, thoracic and mediastinal disorders: 
Uncommon: cough 
 
Gastrointestinal disorders: 
Common: nausea/vomiting 
Uncommon: diarrhoea, dyspepsia/heartburn 
 
Musculoskeletal and connective tissue disorders: 
Common: musculoskeletal pain* 
 
Vascular disorders: 
Common: orthostatic hypotension* 
Uncommon: flushing 
 
General disorders and administration site conditions: 
Common: fatigue 
Uncommon: chest pain 
 
Reproductive system and breast disorders: 
Uncommon: sexual dysfunction 
 
The following additional adverse reactions have been reported during post–marketing 
experience; they are derived from spontaneous reports and therefore, the frequency of these 
adverse reactions is not known: 
 
Nervous system disorders: 
Headache 
 
Ear and labyrinth disorders: 
Tinnitus  
 

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Gastrointestinal disorders: 
Dysgeusia 
 
Renal and urinary disorders: 
Impaired renal function including cases of renal failure in patients at risk (see section 4.4) 
 
Skin and subcutaneous tissue disorders: 
Leukocytoclastic vasculitis 
 
Musculoskeletal and connective tissue disorders: 
Arthralgia, myalgia (in some cases associated with increased plasma creatine kinase levels), muscle 
cramps 
 
Metabolism and nutrition disorders: 
Hyperkalaemia 
 
Immune system disorders: 
Hypersensitivity reactions such as angioedema, rash, urticaria 
 
Hepato-biliary disorders: 
Hepatitis, abnormal liver function 
 
Paediatric patients: in a randomised trial of 318 hypertensive children and adolescents aged 6 to 
16 years, the following related adverse events 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. 
 
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 
Irbesartan BMS. 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. 
 

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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 BMS 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 BMS 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. 
 
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 
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 BMS, 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 BMS 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 BMS, 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 

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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 BMS 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 
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 BMS 300 mg group (34%) than in the placebo group (21%). 
 
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). 

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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. 
 
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. 
 
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 
 
Microcrystalline cellulose 
Croscarmellose sodium 
Lactose monohydrate 
Magnesium stearate 
Colloidal hydrated silica 
Pregelatinised maize starch 
Poloxamer 188 
 

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6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years. 
 
6.4 Special precautions for storage 
 
Do not store above 30°C. 
 
6.5 Nature and contents of container 
 
Cartons of 14 tablets: 1 blister card of 14 tablets in PVC/PVDC/Aluminium blisters. 
Cartons of 28 tablets: 2 blister cards of 14 tablets in PVC/PVDC/Aluminium blisters. 
Cartons of 56 tablets: 4 blister cards of 14 tablets in PVC/PVDC/Aluminium blisters. 
Cartons of 98 tablets: 7 blister cards of 14 tablets in PVC/PVDC/Aluminium blisters. 
Cartons of 56 x 1 tablet; 7 blister cards of 8 x 1 tablet each in PVC/PVDC/Aluminium perforated unit 
dose 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 
 
BRISTOL-MYERS SQUIBB PHARMA EEIG 
Uxbridge Business Park 
Sanderson Road 
Uxbridge UB8 1DH - United Kingdom 
 
 
8. MARKETING AUTHORISATION NUMBERS 
 
EU/1/06/375/006-010 
 
 
9. DATE OF FIRST AUTHORISATION / RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 19 January 2007 
Date of latest renewal: 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this product is available on the website of the European Medicines Agency 
(EMEA) http://www.emea.europa.eu/ 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Irbesartan BMS 300 mg tablets. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each tablet contains 300 mg of irbesartan. 
 
Excipient: 61.50 mg of lactose monohydrate per tablet. 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Tablet. 
White to off-white, biconvex, and oval-shaped with a heart debossed on one side and the number 2773 
engraved on the other side. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Treatment of essential hypertension. 
Treatment of renal disease in patients with hypertension and type 2 diabetes mellitus as part of an 
antihypertensive medicinal product regimen (see section 5.1). 
 
4.2 Posology and method of administration 
 
The usual recommended initial and maintenance dose is 150 mg once daily, with or without food. 
Irbesartan BMS 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 Irbesartan BMS can be 
increased to 300 mg, or other antihypertensive agents can be added. In particular, the addition of a 
diuretic such as hydrochlorothiazide has been shown to have an additive effect with Irbesartan BMS 
(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 Irbesartan BMS 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 section 5.1). 
 
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 
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. 
 

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Paediatric patients: irbesartan is not recommended for use in children and adolescents due to 
insufficient data on safety and efficacy (see sections 4.8, 5.1 and 5.2). 
 
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). 
 
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 Irbesartan 
BMS. 
 
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 Irbesartan BMS, a similar effect should be anticipated with angiotensin-II 
receptor antagonists. 
 
Renal impairment and kidney transplantation: when Irbesartan BMS 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 Irbesartan BMS 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). 
 
Hyperkalaemia: as with other medicinal products that affect the renin-angiotensin-aldosterone system, 
hyperkalaemia may occur during the treatment with Irbesartan BMS, 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). 
 
Lithium: the combination of lithium and Irbesartan BMS 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 Irbesartan BMS 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). 

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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 patients: 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 BMS 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 Irbesartan BMS (see section 4.4). 
 
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 
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. 
 

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4.6 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). 
 
Lactation: 
 
Because no information is available regarding the use of Irbesartan BMS during breast-feeding, 
Irbesartan BMS is not recommended and alternative treatments with better established safety profiles 
during breast-feeding are preferable, especially while nursing a newborn or preterm infant. 
 
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: 

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very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, 
< 1/1,000); very rare (< 1/10,000). Within each frequency grouping, undesirable effects are presented 
in order of decreasing seriousness. 
 
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. 

 
Cardiac disorders: 
Uncommon: tachycardia 
 
Nervous system disorders: 
Common: dizziness, orthostatic dizziness* 
 
Respiratory, thoracic and mediastinal disorders: 
Uncommon: cough 
 
Gastrointestinal disorders: 
Common: nausea/vomiting 
Uncommon: diarrhoea, dyspepsia/heartburn 
 
Musculoskeletal and connective tissue disorders: 
Common: musculoskeletal pain* 
 
Vascular disorders: 
Common: orthostatic hypotension* 
Uncommon: flushing 
 
General disorders and administration site conditions: 
Common: fatigue 
Uncommon: chest pain 
 
Reproductive system and breast disorders: 
Uncommon: sexual dysfunction 
 
The following additional adverse reactions have been reported during post–marketing 
experience; they are derived from spontaneous reports and therefore, the frequency of these 
adverse reactions is not known: 
 
Nervous system disorders: 
Headache 
 
Ear and labyrinth disorders: 
Tinnitus  
 

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Gastrointestinal disorders: 
Dysgeusia 
 
Renal and urinary disorders: 
Impaired renal function including cases of renal failure in patients at risk (see section 4.4) 
 
Skin and subcutaneous tissue disorders: 
Leukocytoclastic vasculitis 
 
Musculoskeletal and connective tissue disorders: 
Arthralgia, myalgia (in some cases associated with increased plasma creatine kinase levels), muscle 
cramps 
 
Metabolism and nutrition disorders: 
Hyperkalaemia 
 
Immune system disorders: 
Hypersensitivity reactions such as angioedema, rash, urticaria 
 
Hepato-biliary disorders: 
Hepatitis, abnormal liver function 
 
Paediatric patients: in a randomised trial of 318 hypertensive children and adolescents aged 6 to 
16 years, the following related adverse events 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. 
 
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 
Irbesartan BMS. 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. 
 

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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 BMS 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 BMS 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. 
 
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 
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 BMS, 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 BMS 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 BMS, 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 

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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 BMS 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 
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 BMS 300 mg group (34%) than in the placebo group (21%). 
 
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). 

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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. 
 
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. 
 
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 
 
Microcrystalline cellulose 
Croscarmellose sodium 
Lactose monohydrate 
Magnesium stearate 
Colloidal hydrated silica 
Pregelatinised maize starch 
Poloxamer 188 
 

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6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years. 
 
6.4 Special precautions for storage 
 
Do not store above 30°C. 
 
6.5 Nature and contents of container 
 
Cartons of 14 tablets: 1 blister card of 14 tablets in PVC/PVDC/Aluminium blisters. 
Cartons of 28 tablets: 2 blister cards of 14 tablets in PVC/PVDC/Aluminium blisters. 
Cartons of 56 tablets: 4 blister cards of 14 tablets in PVC/PVDC/Aluminium blisters. 
Cartons of 98 tablets: 7 blister cards of 14 tablets in PVC/PVDC/Aluminium blisters. 
Cartons of 56 x 1 tablet; 7 blister cards of 8 x 1 tablet each in PVC/PVDC/Aluminium perforated unit 
dose 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 
 
BRISTOL-MYERS SQUIBB PHARMA EEIG 
Uxbridge Business Park 
Sanderson Road 
Uxbridge UB8 1DH - United Kingdom 
 
 
8. MARKETING AUTHORISATION NUMBERS 
 
EU/1/06/375/011-015 
 
 
9. DATE OF FIRST AUTHORISATION / RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 19 January 2007 
Date of latest renewal: 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this product is available on the website of the European Medicines Agency 
(EMEA) http://www.emea.europa.eu/ 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Irbesartan BMS 75 mg film-coated tablets. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 75 mg of irbesartan. 
 
Excipient: 25.50 mg of lactose monohydrate per film-coated tablet. 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet. 
White to off-white, biconvex, and oval-shaped with a heart debossed on one side and the number 2871 
engraved on the other side. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Treatment of essential hypertension. 
Treatment of renal disease in patients with hypertension and type 2 diabetes mellitus as part of an 
antihypertensive medicinal product regimen (see section 5.1). 
 
4.2 Posology and method of administration 
 
The usual recommended initial and maintenance dose is 150 mg once daily, with or without food. 
Irbesartan BMS 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 Irbesartan BMS can be 
increased to 300 mg, or other antihypertensive agents can be added. In particular, the addition of a 
diuretic such as hydrochlorothiazide has been shown to have an additive effect with Irbesartan BMS 
(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 Irbesartan BMS 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 section 5.1). 
 
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 
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. 
 

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Paediatric patients: irbesartan is not recommended for use in children and adolescents due to 
insufficient data on safety and efficacy (see sections 4.8, 5.1 and 5.2). 
 
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). 
 
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 Irbesartan 
BMS. 
 
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 Irbesartan BMS, a similar effect should be anticipated with angiotensin-II 
receptor antagonists. 
 
Renal impairment and kidney transplantation: when Irbesartan BMS 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 Irbesartan BMS 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). 
 
Hyperkalaemia: as with other medicinal products that affect the renin-angiotensin-aldosterone system, 
hyperkalaemia may occur during the treatment with Irbesartan BMS, 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). 
 
Lithium: the combination of lithium and Irbesartan BMS 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 Irbesartan BMS 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). 

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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 patients: 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 BMS 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 Irbesartan BMS (see section 4.4). 
 
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 
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. 
 

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4.6 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). 
 
Lactation: 
 
Because no information is available regarding the use of Irbesartan BMS during breast-feeding, 
Irbesartan BMS is not recommended and alternative treatments with better established safety profiles 
during breast-feeding are preferable, especially while nursing a newborn or preterm infant. 
 
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: 

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very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, 
< 1/1,000); very rare (< 1/10,000). Within each frequency grouping, undesirable effects are presented 
in order of decreasing seriousness. 
 
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. 

 
Cardiac disorders: 
Uncommon: tachycardia 
 
Nervous system disorders: 
Common: dizziness, orthostatic dizziness* 
 
Respiratory, thoracic and mediastinal disorders: 
Uncommon: cough 
 
Gastrointestinal disorders: 
Common: nausea/vomiting 
Uncommon: diarrhoea, dyspepsia/heartburn 
 
Musculoskeletal and connective tissue disorders:  
Common: musculoskeletal pain* 
 
Vascular disorders: 
Common: orthostatic hypotension* 
Uncommon: flushing 
 
General disorders and administration site conditions: 
Common: fatigue 
Uncommon: chest pain 
 
Reproductive system and breast disorders: 
Uncommon: sexual dysfunction 
 
The following additional adverse reactions have been reported during post–marketing 
experience; they are derived from spontaneous reports and therefore, the frequency of these 
adverse reactions is not known: 
 
Nervous system disorders: 
Headache 
 
Ear and labyrinth disorders: 
Tinnitus  
 

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Gastrointestinal disorders: 
Dysgeusia 
 
Renal and urinary disorders: 
Impaired renal function including cases of renal failure in patients at risk (see section 4.4) 
 
Skin and subcutaneous tissue disorders: 
Leukocytoclastic vasculitis 
 
Musculoskeletal and connective tissue disorders: 
Arthralgia, myalgia (in some cases associated with increased plasma creatine kinase levels), muscle 
cramps 
 
Metabolism and nutrition disorders: 
Hyperkalaemia 
 
Immune system disorders: 
Hypersensitivity reactions such as angioedema, rash, urticaria 
 
Hepato-biliary disorders: 
Hepatitis, abnormal liver function 
 
Paediatric patients: in a randomised trial of 318 hypertensive children and adolescents aged 6 to 
16 years, the following related adverse events 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. 
 
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 
Irbesartan BMS. 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. 
 

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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 BMS 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 BMS 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. 
 
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 
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 BMS, 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 BMS 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 BMS, 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 

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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 BMS 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 
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 BMS 300 mg group (34%) than in the placebo group (21%). 
 
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 

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(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. 
 
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. 
 
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 
Hypromellose 
Silicon dioxide 
Magnesium stearate. 
 

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Film-coating: 
Lactose monohydrate 
Hypromellose 
Titanium dioxide 
Macrogol 3000 
Carnauba wax. 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years. 
 
6.4 Special precautions for storage 
 
Do not store above 30°C. 
 
6.5 Nature and contents of container 
 
Cartons of 14 film-coated tablets: 1 blister card of 14 film-coated tablets in PVC/PVDC/Aluminium 
blisters. 
Cartons of 28 film-coated tablets: 2 blister cards of 14 film-coated tablets in PVC/PVDC/Aluminium 
blisters. 
Cartons of 56 film-coated tablets: 4 blister cards of 14 film-coated tablets in PVC/PVDC/Aluminium 
blisters. 
Cartons of 84 film-coated tablets: 6 blister cards of 14 film-coated tablets in PVC/PVDC/Aluminium 
blisters. 
Cartons of 98 film-coated tablets: 7 blister cards of 14 film-coated tablets in PVC/PVDC/Aluminium 
blisters. 
Cartons of 56 x 1 film-coated tablet; 7 blister cards of 8 x 1 film-coated tablet each in 
PVC/PVDC/Aluminium perforated unit dose 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 
 
BRISTOL-MYERS SQUIBB PHARMA EEIG 
Uxbridge Business Park 
Sanderson Road 
Uxbridge UB8 1DH - United Kingdom 
 
 
8. MARKETING AUTHORISATION NUMBERS 
 
EU/1/06/375/016-021 
 
 

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9. DATE OF FIRST AUTHORISATION / RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 19 January 2007 
Date of latest renewal: 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this product is available on the website of the European Medicines Agency 
(EMEA) http://www.emea.europa.eu/ 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Irbesartan BMS 150 mg film-coated tablets. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 150 mg of irbesartan. 
 
Excipient: 51.00 mg of lactose monohydrate per film-coated tablet. 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet. 
White to off-white, biconvex, and oval-shaped with a heart debossed on one side and the number 2872 
engraved on the other side. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Treatment of essential hypertension. 
Treatment of renal disease in patients with hypertension and type 2 diabetes mellitus as part of an 
antihypertensive medicinal product regimen (see section 5.1). 
 
4.2 Posology and method of administration 
 
The usual recommended initial and maintenance dose is 150 mg once daily, with or without food. 
Irbesartan BMS 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 Irbesartan BMS can be 
increased to 300 mg, or other antihypertensive agents can be added. In particular, the addition of a 
diuretic such as hydrochlorothiazide has been shown to have an additive effect with Irbesartan BMS 
(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 Irbesartan BMS 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 section 5.1). 
 
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 
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. 
 

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Paediatric patients: irbesartan is not recommended for use in children and adolescents due to 
insufficient data on safety and efficacy (see sections 4.8, 5.1 and 5.2). 
 
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). 
 
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 Irbesartan 
BMS. 
 
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 Irbesartan BMS, a similar effect should be anticipated with angiotensin-II 
receptor antagonists. 
 
Renal impairment and kidney transplantation: when Irbesartan BMS 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 Irbesartan BMS 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). 
 
Hyperkalaemia: as with other medicinal products that affect the renin-angiotensin-aldosterone system, 
hyperkalaemia may occur during the treatment with Irbesartan BMS, 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). 
 
Lithium: the combination of lithium and Irbesartan BMS 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 Irbesartan BMS 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). 

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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 patients: 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 BMS 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 Irbesartan BMS (see section 4.4). 
 
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 
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. 
 

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4.6 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). 
 
Lactation: 
 
Because no information is available regarding the use of Irbesartan BMS during breast-feeding, 
Irbesartan BMS is not recommended and alternative treatments with better established safety profiles 
during breast-feeding are preferable, especially while nursing a newborn or preterm infant. 
 
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: 

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very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, 
< 1/1,000); very rare (< 1/10,000). Within each frequency grouping, undesirable effects are presented 
in order of decreasing seriousness. 
 
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. 

 
Cardiac disorders: 
Uncommon: tachycardia 
 
Nervous system disorders: 
Common: dizziness, orthostatic dizziness* 
 
Respiratory, thoracic and mediastinal disorders: 
Uncommon: cough 
 
Gastrointestinal disorders: 
Common: nausea/vomiting 
Uncommon: diarrhoea, dyspepsia/heartburn 
 
Musculoskeletal and connective tissue disorders:  
Common: musculoskeletal pain* 
 
Vascular disorders: 
Common: orthostatic hypotension* 
Uncommon: flushing 
 
General disorders and administration site conditions: 
Common: fatigue 
Uncommon: chest pain 
 
Reproductive system and breast disorders: 
Uncommon: sexual dysfunction 
 
The following additional adverse reactions have been reported during post–marketing 
experience; they are derived from spontaneous reports and therefore, the frequency of these 
adverse reactions is not known: 
 
Nervous system disorders: 
Headache 
 
Ear and labyrinth disorders: 
Tinnitus  
 

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Gastrointestinal disorders: 
Dysgeusia 
 
Renal and urinary disorders: 
Impaired renal function including cases of renal failure in patients at risk (see section 4.4) 
 
Skin and subcutaneous tissue disorders: 
Leukocytoclastic vasculitis 
 
Musculoskeletal and connective tissue disorders: 
Arthralgia, myalgia (in some cases associated with increased plasma creatine kinase levels), muscle 
cramps 
 
Metabolism and nutrition disorders: 
Hyperkalaemia 
 
Immune system disorders: 
Hypersensitivity reactions such as angioedema, rash, urticaria 
 
Hepato-biliary disorders: 
Hepatitis, abnormal liver function 
 
Paediatric patients: in a randomised trial of 318 hypertensive children and adolescents aged 6 to 
16 years, the following related adverse events 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. 
 
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 
Irbesartan BMS. 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. 
 

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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 BMS 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 BMS 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. 
 
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 
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 BMS, 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 BMS 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 BMS, 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 

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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 BMS 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 
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 BMS 300 mg group (34%) than in the placebo group (21%). 
 
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 

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(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. 
 
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. 
 
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 
Hypromellose 
Silicon dioxide 
Magnesium stearate. 
 

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Film-coating: 
Lactose monohydrate 
Hypromellose 
Titanium dioxide 
Macrogol 3000 
Carnauba wax. 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years. 
 
6.4 Special precautions for storage 
 
Do not store above 30°C. 
 
6.5 Nature and contents of container 
 
Cartons of 14 film-coated tablets: 1 blister card of 14 film-coated tablets in PVC/PVDC/Aluminium 
blisters. 
Cartons of 28 film-coated tablets: 2 blister cards of 14 film-coated tablets in PVC/PVDC/Aluminium 
blisters. 
Cartons of 56 film-coated tablets: 4 blister cards of 14 film-coated tablets in PVC/PVDC/Aluminium 
blisters. 
Cartons of 84 film-coated tablets: 6 blister cards of 14 film-coated tablets in PVC/PVDC/Aluminium 
blisters. 
Cartons of 98 film-coated tablets: 7 blister cards of 14 film-coated tablets in PVC/PVDC/Aluminium 
blisters. 
Cartons of 56 x 1 film-coated tablet; 7 blister cards of 8 x 1 film-coated tablet each in 
PVC/PVDC/Aluminium perforated unit dose 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 
 
BRISTOL-MYERS SQUIBB PHARMA EEIG 
Uxbridge Business Park 
Sanderson Road 
Uxbridge UB8 1DH - United Kingdom 
 
 
8. MARKETING AUTHORISATION NUMBERS 
 
EU/1/06/375/022-027 
 
 

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9. DATE OF FIRST AUTHORISATION / RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 19 January 2007 
Date of latest renewal: 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this product is available on the website of the European Medicines Agency 
(EMEA) http://www.emea.europa.eu/ 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Irbesartan BMS 300 mg film-coated tablets. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 300 mg of irbesartan. 
 
Excipient: 102.00 mg of lactose monohydrate per film-coated tablet. 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet. 
White to off-white, biconvex, and oval-shaped with a heart debossed on one side and the number 2873 
engraved on the other side. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Treatment of essential hypertension. 
Treatment of renal disease in patients with hypertension and type 2 diabetes mellitus as part of an 
antihypertensive medicinal product regimen (see section 5.1). 
 
4.2 Posology and method of administration 
 
The usual recommended initial and maintenance dose is 150 mg once daily, with or without food. 
Irbesartan BMS 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 Irbesartan BMS can be 
increased to 300 mg, or other antihypertensive agents can be added. In particular, the addition of a 
diuretic such as hydrochlorothiazide has been shown to have an additive effect with Irbesartan BMS 
(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 Irbesartan BMS 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 section 5.1). 
 
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 
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. 
 

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Paediatric patients: irbesartan is not recommended for use in children and adolescents due to 
insufficient data on safety and efficacy (see sections 4.8, 5.1 and 5.2). 
 
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). 
 
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 Irbesartan 
BMS. 
 
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 Irbesartan BMS, a similar effect should be anticipated with angiotensin-II 
receptor antagonists. 
 
Renal impairment and kidney transplantation: when Irbesartan BMS 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 Irbesartan BMS 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). 
 
Hyperkalaemia: as with other medicinal products that affect the renin-angiotensin-aldosterone system, 
hyperkalaemia may occur during the treatment with Irbesartan BMS, 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). 
 
Lithium: the combination of lithium and Irbesartan BMS 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 Irbesartan BMS 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). 

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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 patients: 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 BMS 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 Irbesartan BMS (see section 4.4). 
 
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 
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. 
 

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4.6 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). 
 
Lactation: 
 
Because no information is available regarding the use of Irbesartan BMS during breast-feeding, 
Irbesartan BMS is not recommended and alternative treatments with better established safety profiles 
during breast-feeding are preferable, especially while nursing a newborn or preterm infant. 
 
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: 

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very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, 
< 1/1,000); very rare (< 1/10,000). Within each frequency grouping, undesirable effects are presented 
in order of decreasing seriousness. 
 
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. 

 
Cardiac disorders: 
Uncommon: tachycardia 
 
Nervous system disorders: 
Common: dizziness, orthostatic dizziness* 
 
Respiratory, thoracic and mediastinal disorders: 
Uncommon: cough 
 
Gastrointestinal disorders: 
Common: nausea/vomiting 
Uncommon: diarrhoea, dyspepsia/heartburn 
 
Musculoskeletal and connective tissue disorders:  
Common: musculoskeletal pain* 
 
Vascular disorders: 
Common: orthostatic hypotension* 
Uncommon: flushing 
 
General disorders and administration site conditions: 
Common: fatigue 
Uncommon: chest pain 
 
Reproductive system and breast disorders: 
Uncommon: sexual dysfunction 
 
The following additional adverse reactions have been reported during post–marketing 
experience; they are derived from spontaneous reports and therefore, the frequency of these 
adverse reactions is not known: 
 
Nervous system disorders: 
Headache 
 
Ear and labyrinth disorders: 
Tinnitus  
 

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Gastrointestinal disorders: 
Dysgeusia 
 
Renal and urinary disorders: 
Impaired renal function including cases of renal failure in patients at risk (see section 4.4) 
 
Skin and subcutaneous tissue disorders: 
Leukocytoclastic vasculitis 
 
Musculoskeletal and connective tissue disorders: 
Arthralgia, myalgia (in some cases associated with increased plasma creatine kinase levels), muscle 
cramps 
 
Metabolism and nutrition disorders: 
Hyperkalaemia 
 
Immune system disorders: 
Hypersensitivity reactions such as angioedema, rash, urticaria 
 
Hepato-biliary disorders: 
Hepatitis, abnormal liver function 
 
Paediatric patients: in a randomised trial of 318 hypertensive children and adolescents aged 6 to 
16 years, the following related adverse events 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. 
 
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 
Irbesartan BMS. 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. 
 

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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 BMS 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 BMS 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. 
 
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 
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 BMS, 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 BMS 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 BMS, 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 

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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 BMS 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 
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 BMS 300 mg group (34%) than in the placebo group (21%). 
 
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 

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(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. 
 
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. 
 
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 
Hypromellose 
Silicon dioxide 
Magnesium stearate. 
 

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Film-coating: 
Lactose monohydrate 
Hypromellose 
Titanium dioxide 
Macrogol 3000 
Carnauba wax. 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years. 
 
6.4 Special precautions for storage 
 
Do not store above 30°C. 
 
6.5 Nature and contents of container 
 
Cartons of 14 film-coated tablets: 1 blister card of 14 film-coated tablets in PVC/PVDC/Aluminium 
blisters. 
Cartons of 28 film-coated tablets: 2 blister cards of 14 film-coated tablets in PVC/PVDC/Aluminium 
blisters. 
Cartons of 56 film-coated tablets: 4 blister cards of 14 film-coated tablets in PVC/PVDC/Aluminium 
blisters. 
Cartons of 84 film-coated tablets: 6 blister cards of 14 film-coated tablets in PVC/PVDC/Aluminium 
blisters. 
Cartons of 98 film-coated tablets: 7 blister cards of 14 film-coated tablets in PVC/PVDC/Aluminium 
blisters. 
Cartons of 56 x 1 film-coated tablet; 7 blister cards of 8 x 1 film-coated tablet each in 
PVC/PVDC/Aluminium perforated unit dose 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 
 
BRISTOL-MYERS SQUIBB PHARMA EEIG 
Uxbridge Business Park 
Sanderson Road 
Uxbridge UB8 1DH - United Kingdom 
 
 
8. MARKETING AUTHORISATION NUMBERS 
 
EU/1/06/375/028-033 
 
 

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9. DATE OF FIRST AUTHORISATION / RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 19 January 2007 
Date of latest renewal: 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this product is available on the website of the European Medicines Agency 
(EMEA) http://www.emea.europa.eu/ 
 

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ANNEX II 
 

A. MANUFACTURING AUTHORISATION HOLDERS RESPONSIBLE FOR 
BATCH RELEASE 

 
B. CONDITIONS OF THE MARKETING AUTHORISATION 

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A. MANUFACTURING AUTHORISATION HOLDERS RESPONSIBLE FOR BATCH 
RELEASE 

 
Name and address of the manufacturers responsible for batch release 
 
Sanofi Winthrop Industrie 
1 rue de la Vierge 
Ambarès & Lagrave 
F-33565 Carbon Blanc Cedex 
France 
 
Sanofi-Synthelabo Limited 
Edgefield Avenue, 
Fawdon 
Newcastle Upon Tyne, 
Tyne & Wear NE3 3TT 
United Kingdom 
 
Sanofi Winthrop Industrie 
30-36 Avenue Gustave Eiffel, BP 7166 
F-37071 Tours Cedex 2 
France 
 
Chinoin Private Co. Ltd. 
Lévai u.5. 
2112 Veresegyhaz 
Hungary 
 
 
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 OF THE MARKETING AUTHORISATION 
 
 CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON 

THE MARKETING AUTHORISATION HOLDER 
 
Medicinal product subject to medical prescription 
 
 CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
Not applicable. 
 
 OTHER CONDITIONS 

 
The PSUR cycle of Irbesartan BMS is aligned with the cross-referred product, KARVEA, until 
otherwise specified. 
 
Pharmacovigilance system 
The MAH must ensure that the system of pharmacovigilance, as described in version 3.0 presented in 
Module 1.8.1. of the Marketing Authorisation Application, is in place and functioning before and 
whilst the product is on the market. 
 

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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 
 
Irbesartan BMS 75 mg tablets 
irbesartan 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains: irbesartan 75 mg 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: also contains lactose monohydrate. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
14 tablets 
28 tablets 
56 tablets 
56 x 1 tablets 
98 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 REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 30°C. 
 
 

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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 
 
BRISTOL-MYERS SQUIBB PHARMA EEIG 
Uxbridge Business Park 
Sanderson Road 
Uxbridge UB8 1DH - United Kingdom 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/375/001 - 14 tablets 
EU/1/06/375/002 - 28 tablets 
EU/1/06/375/003 - 56 tablets 
EU/1/06/375/004 - 56 x 1 tablets 
EU/1/06/375/005 - 98 tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Irbesartan BMS 75 mg 

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Irbesartan BMS 75 mg tablets 
irbesartan 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
BRISTOL-MYERS SQUIBB PHARMA EEIG 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
14 - 28 - 56 - 98 tablets: 
Mon 
Tue 
Wed 
Thu 
Fri 
Sat 
Sun 
 
56 x 1 tablets: 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Irbesartan BMS 150 mg tablets 
irbesartan 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains: irbesartan 150 mg 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: also contains lactose monohydrate. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
14 tablets 
28 tablets 
56 tablets 
56 x 1 tablets 
98 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 REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 30°C. 
 
 

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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 
 
BRISTOL-MYERS SQUIBB PHARMA EEIG 
Uxbridge Business Park 
Sanderson Road 
Uxbridge UB8 1DH - United Kingdom 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/375/006 - 14 tablets 
EU/1/06/375/007 - 28 tablets 
EU/1/06/375/008 - 56 tablets 
EU/1/06/375/009 - 56 x 1 tablets 
EU/1/06/375/010 - 98 tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Irbesartan BMS 150 mg 

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Irbesartan BMS 150 mg tablets 
irbesartan 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
BRISTOL-MYERS SQUIBB PHARMA EEIG 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
14 - 28 - 56 - 98 tablets: 
Mon 
Tue 
Wed 
Thu 
Fri 
Sat 
Sun 
 
56 x 1 tablets: 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Irbesartan BMS 300 mg tablets 
irbesartan 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains: irbesartan 300 mg 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: also contains lactose monohydrate. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
14 tablets 
28 tablets 
56 tablets 
56 x 1 tablets 
98 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 REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 30°C. 
 
 

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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 
 
BRISTOL-MYERS SQUIBB PHARMA EEIG 
Uxbridge Business Park 
Sanderson Road 
Uxbridge UB8 1DH - United Kingdom 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/375/011 - 14 tablets 
EU/1/06/375/012 - 28 tablets 
EU/1/06/375/013 - 56 tablets 
EU/1/06/375/014 - 56 x 1 tablets 
EU/1/06/375/015 - 98 tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Irbesartan BMS 300 mg 

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Irbesartan BMS 300 mg tablets 
irbesartan 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
BRISTOL-MYERS SQUIBB PHARMA EEIG 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
14 - 28 - 56 - 98 tablets: 
Mon 
Tue 
Wed 
Thu 
Fri 
Sat 
Sun 
 
56 x 1 tablets: 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Irbesartan BMS 75 mg film-coated tablets 
irbesartan 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains: irbesartan 75 mg 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: also contains lactose monohydrate. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
14 tablets 
28 tablets 
56 tablets 
56 x 1 tablets 
84 tablets 
98 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 REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 30°C. 
 
 

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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 
 
BRISTOL-MYERS SQUIBB PHARMA EEIG 
Uxbridge Business Park 
Sanderson Road 
Uxbridge UB8 1DH - United Kingdom 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/375/016 - 14 tablets 
EU/1/06/375/017 - 28 tablets 
EU/1/06/375/018 - 56 tablets 
EU/1/06/375/019 - 56 x 1 tablets 
EU/1/06/375/020 - 84 tablets 
EU/1/06/375/021 - 98 tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Irbesartan BMS 75 mg 

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Irbesartan BMS 75 mg tablets 
irbesartan 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
BRISTOL-MYERS SQUIBB PHARMA EEIG 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
14 - 28 - 56 - 84 - 98 tablets: 
Mon 
Tue 
Wed 
Thu 
Fri 
Sat 
Sun 
 
56 x 1 tablets: 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Irbesartan BMS 150 mg film-coated tablets 
irbesartan 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains: irbesartan 150 mg 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: also contains lactose monohydrate. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
14 tablets 
28 tablets 
56 tablets 
56 x 1 tablets 
84 tablets 
98 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 REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 30°C. 
 
 

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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 
 
BRISTOL-MYERS SQUIBB PHARMA EEIG 
Uxbridge Business Park 
Sanderson Road 
Uxbridge UB8 1DH - United Kingdom 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/375/022 - 14 tablets 
EU/1/06/375/023 - 28 tablets 
EU/1/06/375/024 - 56 tablets 
EU/1/06/375/025 - 56 x 1 tablets 
EU/1/06/375/026 - 84 tablets 
EU/1/06/375/027 - 98 tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Irbesartan BMS 150 mg 

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Irbesartan BMS 150 mg tablets 
irbesartan 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
BRISTOL-MYERS SQUIBB PHARMA EEIG 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
14 - 28 - 56 - 84 - 98 tablets: 
Mon 
Tue 
Wed 
Thu 
Fri 
Sat 
Sun 
 
56 x 1 tablets: 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Irbesartan BMS 300 mg film-coated tablets 
irbesartan 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains: irbesartan 300 mg 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: also contains lactose monohydrate. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
14 tablets 
28 tablets 
56 tablets 
56 x 1 tablets 
84 tablets 
98 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 REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 30°C. 
 
 

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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 
 
BRISTOL-MYERS SQUIBB PHARMA EEIG 
Uxbridge Business Park 
Sanderson Road 
Uxbridge UB8 1DH - United Kingdom 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/375/028 - 14 tablets 
EU/1/06/375/029 - 28 tablets 
EU/1/06/375/030 - 56 tablets 
EU/1/06/375/031 - 56 x 1 tablets 
EU/1/06/375/032 - 84 tablets 
EU/1/06/375/033 - 98 tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Irbesartan BMS 300 mg 

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Irbesartan BMS 300 mg tablets 
irbesartan 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
BRISTOL-MYERS SQUIBB PHARMA EEIG 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
14 - 28 - 56 - 84 - 98 tablets: 
Mon 
Tue 
Wed 
Thu 
Fri 
Sat 
Sun 
 
56 x 1 tablets: 
 

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B. PACKAGE LEAFLET 

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PACKAGE LEAFLET: INFORMATION FOR THE USER 
Irbesartan BMS 75 mg 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 Irbesartan BMS is and what it is used for 
2. Before you take Irbesartan BMS 
3. How to take Irbesartan BMS 
4. Possible side effects 
5. How to store Irbesartan BMS 
6. Further information 
 
 
1. WHAT IRBESARTAN BMS IS AND WHAT IT IS USED FOR 
 
Irbesartan BMS 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. Irbesartan BMS prevents the binding of 
angiotensin-II to these receptors, causing the blood vessels to relax and the blood pressure to lower. 
Irbesartan BMS slows the decrease of kidney function in patients with high blood pressure and type 2 
diabetes. 
 
Irbesartan BMS is used 
 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 IRBESARTAN BMS 
 
Do not take Irbesartan BMS 
 if you are allergic (hypersensitive) to irbesartan or any other ingredients of Irbesartan BMS 
 if you are more than 3 months pregnant. (It is also better to avoid Irbesartan BMS in early 

pregnancy – see pregnancy section) 
 
Irbesartan BMS should not be given to children and adolescents (under 18 years). 
 
Take special care with Irbesartan BMS 
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 Irbesartan BMS 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 
You must tell your doctor if you think you are (or might become) pregnant. Irbesartan BMS 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). 

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Using other medicines 
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, 
including medicines obtained without a prescription. 
 
Irbesartan BMS does not usually interact with other medicines. 
 
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 Irbesartan BMS with food and drink 
Irbesartan BMS 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 Irbesartan BMS before you become pregnant or as soon as you know you are 
pregnant and will advise you to take another medicine instead of Irbesartan BMS. Irbesartan BMS 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. Irbesartan BMS 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. Irbesartan 
BMS 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 Irbesartan BMS 
Irbesartan BMS 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. 
 
 
3. HOW TO TAKE IRBESARTAN BMS 
 
Always take Irbesartan BMS exactly as your doctor has told you. You should check with your doctor 
or pharmacist if you are not sure. 
 
Method of administration 
Irbesartan BMS is for oral use. Swallow the tablets with a sufficient amount of fluid (e.g. one glass of 
water). You can take Irbesartan BMS 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 Irbesartan BMS until your doctor tells 
you otherwise. 
 
 Patients with high blood pressure 

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

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

In patients with high blood pressure and type 2 diabetes, 300 mg (four tablets a day) 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 Irbesartan BMS than you should 
If you accidentally take too many tablets, contact your doctor immediately. 
 
Children should not take Irbesartan BMS 
Irbesartan BMS 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 Irbesartan BMS 
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, Irbesartan BMS 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 Irbesartan BMS 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 BMS 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 undesirable effects have been reported since marketing of Irbesartan BMS but the frequency for 
them to occur is not known. These undesirable effects are: headache, taste disturbance, ringing in the 
ears, muscle cramps, pain in joints and muscles, abnormal liver function, increased blood potassium 

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levels, impaired kidney function, and inflammation of small blood vessels mainly affecting the skin (a 
condition known as leukocytoclastic vasculitis). 
 
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 IRBESARTAN BMS 
 
Keep out of the reach and sight of children. 
 
Do not use Irbesartan BMS 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. 
 
Do not store above 30°C. 
 
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 Irbesartan BMS contains 
 The active substance is irbesartan. Each tablet of Irbesartan BMS 75 mg contains 75 mg 

irbesartan. 
 The other ingredients are microcrystalline cellulose, croscarmellose sodium, lactose 

monohydrate, magnesium stearate, colloidal hydrated silica, pregelatinised maize starch, and 
poloxamer 188. 

 
What Irbesartan BMS looks like and contents of the pack 
Irbesartan BMS 75 mg tablets are white to off-white, biconvex, and oval-shaped with a heart debossed 
on one side and the number 2771 engraved on the other side. 
 
Irbesartan BMS 75 mg tablets are supplied in blister packs of 14, 28, 56 or 98 tablets. Unidose blister 
packs of 56 x 1 tablet for delivery in hospitals are also available. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder: 
BRISTOL-MYERS SQUIBB PHARMA EEIG 
Uxbridge Business Park 
Sanderson Road 
Uxbridge UB8 1DH - United Kingdom 
 
Manufacturer: 
SANOFI WINTHROP INDUSTRIE 
1, rue de la Vierge 
Ambarès & Lagrave 
F-33565 Carbon Blanc Cedex - France 
 
SANOFI SYNTHELABO LIMITED 
Edgefield Avenue - Fawdon 
Newcastle Upon Tyne, Tyne & Wear NE3 3TT - United Kingdom 
 
SANOFI WINTHROP INDUSTRIE 
30-36 Avenue Gustave Eiffel, BP 7166 
F-37071 Tours Cedex 2 - France 

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For any information about this medicinal product, please contact the local representative of the 
Marketing Authorisation Holder. 
 
Belgique/België/Belgien 
BRISTOL-MYERS SQUIBB BELGIUM S.A./N.V. 
Tél/Tel: + 32 2 352 74 60 
 

Luxembourg/Luxemburg 
BRISTOL-MYERS SQUIBB BELGIUM S.A./N.V. 
Tél/Tel: + 32 2 352 74 60 
 

България 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Teл.: + 359 800 12 400 
 

Magyarország 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Tel.: + 36 1 301 9700 
 

Česká republika 
BRISTOL-MYERS SQUIBB SPOL. S R.O. 
Tel: + 420 221 016 111 
 

Malta 
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 
 

Danmark 
BRISTOL-MYERS SQUIBB 
Tlf: + 45 45 93 05 06 
 

Nederland 
BRISTOL-MYERS SQUIBB BV 
Tel: + 31 34 857 42 22 
 

Deutschland 
BRISTOL-MYERS SQUIBB GMBH & CO. KGAA 
Tel: + 49 89 121 42-0 
 

Norge 
BRISTOL-MYERS SQUIBB NORWAY LTD 
Tlf: + 47 67 55 53 50 
 

Eesti 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Tel: + 372 640 1301 
 

Österreich 
BRISTOL-MYERS SQUIBB GESMBH 
Tel: + 43 1 60 14 30 
 
 

Ελλάδα 
BRISTOL-MYERS SQUIBB A.E. 
Τηλ: + 30 210 6074300 
 

Polska 
BRISTOL-MYERS SQUIBB POLSKA SP. Z O.O. 
Tel.: + 48 22 5796666 
 

España 
BRISTOL-MYERS SQUIBB, S.A. 
Tel: + 34 91 456 53 00 
 
 

Portugal 
BRISTOL-MYERS SQUIBB FARMACÊUTICA 
PORTUGUESA, S.A. 
Tel: + 351 21 440 70 00 
 

France 
BRISTOL-MYERS SQUIBB SARL 
Tél: + 33 (0)810 410 500 
 
 

România 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Tel: + 40 (0)21 272 16 00 
 

Ireland 
BRISTOL-MYERS SQUIBB PHARMACEUTICALS LTD
Tel: + 353 (1 800) 749 749 
 

Slovenija 
BRISTOL-MYERS SQUIBB SPOL. S R.O. 
Tel: + 386 1 236 47 00 
 

Ísland 
VISTOR HF 
Sími: + 354 535 7000 
 

Slovenská republika 
BRISTOL-MYERS SQUIBB SPOL. S R.O. 
Tel: + 421 2 59298411  
 

Italia 
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 
 

Suomi/Finland 
OY BRISTOL-MYERS SQUIBB (FINLAND) AB 
Puh/Tel: + 358 9 251 21 230 
 

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Κύπρος 
ΑΚΗΣ ΠΑΝΑΓΙΩΤΟΥ & ΥΙΟΣ Ε.Π.Ε. 
Τηλ: + 357 22 677038 
 

Sverige 
BRISTOL-MYERS SQUIBB AB 
Tel: + 46 8 704 71 00 
 

Latvija 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Tel: + 371 67 50 21 85 
 

United Kingdom 
BRISTOL-MYERS SQUIBB PHARMACEUTICALS LTD
Tel: + 44 (0800) 731 1736 
 
 

Lietuva 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Tel: + 370 5 2790 762 
 

 

 

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

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PACKAGE LEAFLET: INFORMATION FOR THE USER 
Irbesartan BMS 150 mg 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 Irbesartan BMS is and what it is used for 
2. Before you take Irbesartan BMS 
3. How to take Irbesartan BMS 
4. Possible side effects 
5. How to store Irbesartan BMS 
6. Further information 
 
 
1. WHAT IRBESARTAN BMS IS AND WHAT IT IS USED FOR 
 
Irbesartan BMS 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. Irbesartan BMS prevents the binding of 
angiotensin-II to these receptors, causing the blood vessels to relax and the blood pressure to lower. 
Irbesartan BMS slows the decrease of kidney function in patients with high blood pressure and type 2 
diabetes. 
 
Irbesartan BMS is used 
 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 IRBESARTAN BMS 
 
Do not take Irbesartan BMS 
 if you are allergic (hypersensitive) to irbesartan or any other ingredients of Irbesartan BMS 
 if you are more than 3 months pregnant. (It is also better to avoid Irbesartan BMS in early 

pregnancy – see pregnancy section) 
 
Irbesartan BMS should not be given to children and adolescents (under 18 years). 
 
Take special care with Irbesartan BMS 
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 Irbesartan BMS 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 
You must tell your doctor if you think you are (or might become) pregnant. Irbesartan BMS 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). 

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Using other medicines 
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, 
including medicines obtained without a prescription. 
 
Irbesartan BMS does not usually interact with other medicines. 
 
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 Irbesartan BMS with food and drink 
Irbesartan BMS 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 Irbesartan BMS before you become pregnant or as soon as you know you are 
pregnant and will advise you to take another medicine instead of Irbesartan BMS. Irbesartan BMS 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. Irbesartan BMS 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. Irbesartan 
BMS 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 Irbesartan BMS 
Irbesartan BMS 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. 
 
 
3. HOW TO TAKE IRBESARTAN BMS 
 
Always take Irbesartan BMS exactly as your doctor has told you. You should check with your doctor 
or pharmacist if you are not sure. 
 
Method of administration 
Irbesartan BMS is for oral use. Swallow the tablets with a sufficient amount of fluid (e.g. one glass of 
water). You can take Irbesartan BMS 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 Irbesartan BMS 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 (two tablets a 
day) once daily depending on blood pressure response. 

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

In patients with high blood pressure and type 2 diabetes, 300 mg (two tablets a day) 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 Irbesartan BMS than you should 
If you accidentally take too many tablets, contact your doctor immediately. 
 
Children should not take Irbesartan BMS 
Irbesartan BMS 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 Irbesartan BMS 
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, Irbesartan BMS 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 Irbesartan BMS 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 BMS 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 undesirable effects have been reported since marketing of Irbesartan BMS but the frequency for 
them to occur is not known. These undesirable effects are: headache, taste disturbance, ringing in the 
ears, muscle cramps, pain in joints and muscles, abnormal liver function, increased blood potassium 

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levels, impaired kidney function, and inflammation of small blood vessels mainly affecting the skin (a 
condition known as leukocytoclastic vasculitis). 
 
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 IRBESARTAN BMS 
 
Keep out of the reach and sight of children. 
 
Do not use Irbesartan BMS 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. 
 
Do not store above 30°C. 
 
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 Irbesartan BMS contains 
 The active substance is irbesartan. Each tablet of Irbesartan BMS 150 mg contains 150 mg 

irbesartan. 
 The other ingredients are microcrystalline cellulose, croscarmellose sodium, lactose 

monohydrate, magnesium stearate, colloidal hydrated silica, pregelatinised maize starch, and 
poloxamer 188. 

 
What Irbesartan BMS looks like and contents of the pack 
Irbesartan BMS 150 mg tablets are white to off-white, biconvex, and oval-shaped with a heart 
debossed on one side and the number 2772 engraved on the other side. 
 
Irbesartan BMS 150 mg tablets are supplied in blister packs of 14, 28, 56 or 98 tablets. Unidose blister 
packs of 56 x 1 tablet for delivery in hospitals are also available. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder: 
BRISTOL-MYERS SQUIBB PHARMA EEIG 
Uxbridge Business Park 
Sanderson Road 
Uxbridge UB8 1DH - United Kingdom 
 
Manufacturer: 
SANOFI WINTHROP INDUSTRIE 
1, rue de la Vierge 
Ambarès & Lagrave 
F-33565 Carbon Blanc Cedex - France 
 
SANOFI SYNTHELABO LIMITED 
Edgefield Avenue - Fawdon 
Newcastle Upon Tyne, Tyne & Wear NE3 3TT - United Kingdom 
 
SANOFI WINTHROP INDUSTRIE 
30-36 Avenue Gustave Eiffel, BP 7166 
F-37071 Tours Cedex 2 - France 

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CHINOIN PRIVATE CO. LTD. 
Lévai u.5. 
2112 Veresegyház - Hungary 

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For any information about this medicinal product, please contact the local representative of the 
Marketing Authorisation Holder. 
 
Belgique/België/Belgien 
BRISTOL-MYERS SQUIBB BELGIUM S.A./N.V. 
Tél/Tel: + 32 2 352 74 60 
 

Luxembourg/Luxemburg 
BRISTOL-MYERS SQUIBB BELGIUM S.A./N.V. 
Tél/Tel: + 32 2 352 74 60 
 

България 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Teл.: + 359 800 12 400 
 

Magyarország 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Tel.: + 36 1 301 9700 
 

Česká republika 
BRISTOL-MYERS SQUIBB SPOL. S R.O. 
Tel: + 420 221 016 111 
 

Malta 
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 
 

Danmark 
BRISTOL-MYERS SQUIBB 
Tlf: + 45 45 93 05 06 
 

Nederland 
BRISTOL-MYERS SQUIBB BV 
Tel: + 31 34 857 42 22 
 

Deutschland 
BRISTOL-MYERS SQUIBB GMBH & CO. KGAA 
Tel: + 49 89 121 42-0 
 

Norge 
BRISTOL-MYERS SQUIBB NORWAY LTD 
Tlf: + 47 67 55 53 50 
 

Eesti 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Tel: + 372 640 1301 
 

Österreich 
BRISTOL-MYERS SQUIBB GESMBH 
Tel: + 43 1 60 14 30 
 
 

Ελλάδα 
BRISTOL-MYERS SQUIBB A.E. 
Τηλ: + 30 210 6074300 
 

Polska 
BRISTOL-MYERS SQUIBB POLSKA SP. Z O.O. 
Tel.: + 48 22 5796666 
 

España 
BRISTOL-MYERS SQUIBB, S.A. 
Tel: + 34 91 456 53 00 
 
 

Portugal 
BRISTOL-MYERS SQUIBB FARMACÊUTICA 
PORTUGUESA, S.A. 
Tel: + 351 21 440 70 00 
 

France 
BRISTOL-MYERS SQUIBB SARL 
Tél: + 33 (0)810 410 500 
 
 

România 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Tel: + 40 (0)21 272 16 00 
 

Ireland 
BRISTOL-MYERS SQUIBB PHARMACEUTICALS LTD
Tel: + 353 (1 800) 749 749 
 

Slovenija 
BRISTOL-MYERS SQUIBB SPOL. S R.O. 
Tel: + 386 1 236 47 00 
 

Ísland 
VISTOR HF 
Sími: + 354 535 7000 
 

Slovenská republika 
BRISTOL-MYERS SQUIBB SPOL. S R.O. 
Tel: + 421 2 59298411  
 

Italia 
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 
 

Suomi/Finland 
OY BRISTOL-MYERS SQUIBB (FINLAND) AB 
Puh/Tel: + 358 9 251 21 230 
 

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Κύπρος 
ΑΚΗΣ ΠΑΝΑΓΙΩΤΟΥ & ΥΙΟΣ Ε.Π.Ε. 
Τηλ: + 357 22 677038 
 

Sverige 
BRISTOL-MYERS SQUIBB AB 
Tel: + 46 8 704 71 00 
 

Latvija 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Tel: + 371 67 50 21 85 
 

United Kingdom 
BRISTOL-MYERS SQUIBB PHARMACEUTICALS LTD
Tel: + 44 (0800) 731 1736 
 
 

Lietuva 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Tel: + 370 5 2790 762 
 

 

 

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

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PACKAGE LEAFLET: INFORMATION FOR THE USER 
Irbesartan BMS 300 mg 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 Irbesartan BMS is and what it is used for 
2. Before you take Irbesartan BMS 
3. How to take Irbesartan BMS 
4. Possible side effects 
5. How to store Irbesartan BMS 
6. Further information 
 
 
1. WHAT IRBESARTAN BMS IS AND WHAT IT IS USED FOR 
 
Irbesartan BMS 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. Irbesartan BMS prevents the binding of 
angiotensin-II to these receptors, causing the blood vessels to relax and the blood pressure to lower. 
Irbesartan BMS slows the decrease of kidney function in patients with high blood pressure and type 2 
diabetes. 
 
Irbesartan BMS is used 
 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 IRBESARTAN BMS 
 
Do not take Irbesartan BMS 
 if you are allergic (hypersensitive) to irbesartan or any other ingredients of Irbesartan BMS 
 if you are more than 3 months pregnant. (It is also better to avoid Irbesartan BMS in early 

pregnancy – see pregnancy section) 
 
Irbesartan BMS should not be given to children and adolescents (under 18 years). 
 
Take special care with Irbesartan BMS 
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 Irbesartan BMS 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 
You must tell your doctor if you think you are (or might become) pregnant. Irbesartan BMS 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). 

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Using other medicines 
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, 
including medicines obtained without a prescription. 
 
Irbesartan BMS does not usually interact with other medicines. 
 
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 Irbesartan BMS with food and drink 
Irbesartan BMS 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 Irbesartan BMS before you become pregnant or as soon as you know you are 
pregnant and will advise you to take another medicine instead of Irbesartan BMS. Irbesartan BMS 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. Irbesartan BMS 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. Irbesartan 
BMS 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 Irbesartan BMS 
Irbesartan BMS 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. 
 
 
3. HOW TO TAKE IRBESARTAN BMS 
 
Always take Irbesartan BMS exactly as your doctor has told you. You should check with your doctor 
or pharmacist if you are not sure. 
 
Method of administration 
Irbesartan BMS is for oral use. Swallow the tablets with a sufficient amount of fluid (e.g. one glass of 
water). You can take Irbesartan BMS 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 Irbesartan BMS 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. 

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 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 Irbesartan BMS than you should 
If you accidentally take too many tablets, contact your doctor immediately. 
 
Children should not take Irbesartan BMS 
Irbesartan BMS 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 Irbesartan BMS 
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, Irbesartan BMS 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 Irbesartan BMS 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 BMS 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 undesirable effects have been reported since marketing of Irbesartan BMS but the frequency for 
them to occur is not known. These undesirable effects are: headache, taste disturbance, ringing in the 
ears, muscle cramps, pain in joints and muscles, abnormal liver function, increased blood potassium 

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levels, impaired kidney function, and inflammation of small blood vessels mainly affecting the skin (a 
condition known as leukocytoclastic vasculitis). 
 
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 IRBESARTAN BMS 
 
Keep out of the reach and sight of children. 
 
Do not use Irbesartan BMS 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. 
 
Do not store above 30°C. 
 
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 Irbesartan BMS contains 
 The active substance is irbesartan. Each tablet of Irbesartan BMS 300 mg contains 300 mg 

irbesartan. 
 The other ingredients are microcrystalline cellulose, croscarmellose sodium, lactose 

monohydrate, magnesium stearate, colloidal hydrated silica, pregelatinised maize starch, and 
poloxamer 188. 

 
What Irbesartan BMS looks like and contents of the pack 
Irbesartan BMS 300 mg tablets are white to off-white, biconvex, and oval-shaped with a heart 
debossed on one side and the number 2773 engraved on the other side. 
 
Irbesartan BMS 300 mg tablets are supplied in blister packs of 14, 28, 56 or 98 tablets. Unidose blister 
packs of 56 x 1 tablet for delivery in hospitals are also available. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder: 
BRISTOL-MYERS SQUIBB PHARMA EEIG 
Uxbridge Business Park 
Sanderson Road 
Uxbridge UB8 1DH - United Kingdom 
 
Manufacturer: 
SANOFI WINTHROP INDUSTRIE 
1, rue de la Vierge 
Ambarès & Lagrave 
F-33565 Carbon Blanc Cedex - France 
 
SANOFI SYNTHELABO LIMITED 
Edgefield Avenue - Fawdon 
Newcastle Upon Tyne, Tyne & Wear NE3 3TT - United Kingdom 
 
SANOFI WINTHROP INDUSTRIE 
30-36 Avenue Gustave Eiffel, BP 7166 
F-37071 Tours Cedex 2 - France 

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CHINOIN PRIVATE CO. LTD. 
Lévai u.5. 
2112 Veresegyház - Hungary 

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For any information about this medicinal product, please contact the local representative of the 
Marketing Authorisation Holder. 
 
Belgique/België/Belgien 
BRISTOL-MYERS SQUIBB BELGIUM S.A./N.V. 
Tél/Tel: + 32 2 352 74 60 
 

Luxembourg/Luxemburg 
BRISTOL-MYERS SQUIBB BELGIUM S.A./N.V. 
Tél/Tel: + 32 2 352 74 60 
 

България 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Teл.: + 359 800 12 400 
 

Magyarország 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Tel.: + 36 1 301 9700 
 

Česká republika 
BRISTOL-MYERS SQUIBB SPOL. S R.O. 
Tel: + 420 221 016 111 
 

Malta 
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 
 

Danmark 
BRISTOL-MYERS SQUIBB 
Tlf: + 45 45 93 05 06 
 

Nederland 
BRISTOL-MYERS SQUIBB BV 
Tel: + 31 34 857 42 22 
 

Deutschland 
BRISTOL-MYERS SQUIBB GMBH & CO. KGAA 
Tel: + 49 89 121 42-0 
 

Norge 
BRISTOL-MYERS SQUIBB NORWAY LTD 
Tlf: + 47 67 55 53 50 
 

Eesti 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Tel: + 372 640 1301 
 

Österreich 
BRISTOL-MYERS SQUIBB GESMBH 
Tel: + 43 1 60 14 30 
 
 

Ελλάδα 
BRISTOL-MYERS SQUIBB A.E. 
Τηλ: + 30 210 6074300 
 

Polska 
BRISTOL-MYERS SQUIBB POLSKA SP. Z O.O. 
Tel.: + 48 22 5796666 
 

España 
BRISTOL-MYERS SQUIBB, S.A. 
Tel: + 34 91 456 53 00 
 
 

Portugal 
BRISTOL-MYERS SQUIBB FARMACÊUTICA 
PORTUGUESA, S.A. 
Tel: + 351 21 440 70 00 
 

France 
BRISTOL-MYERS SQUIBB SARL 
Tél: + 33 (0)810 410 500 
 
 

România 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Tel: + 40 (0)21 272 16 00 
 

Ireland 
BRISTOL-MYERS SQUIBB PHARMACEUTICALS LTD
Tel: + 353 (1 800) 749 749 
 

Slovenija 
BRISTOL-MYERS SQUIBB SPOL. S R.O. 
Tel: + 386 1 236 47 00 
 

Ísland 
VISTOR HF 
Sími: + 354 535 7000 
 

Slovenská republika 
BRISTOL-MYERS SQUIBB SPOL. S R.O. 
Tel: + 421 2 59298411  
 

Italia 
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 
 

Suomi/Finland 
OY BRISTOL-MYERS SQUIBB (FINLAND) AB 
Puh/Tel: + 358 9 251 21 230 
 

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Κύπρος 
ΑΚΗΣ ΠΑΝΑΓΙΩΤΟΥ & ΥΙΟΣ Ε.Π.Ε. 
Τηλ: + 357 22 677038 
 

Sverige 
BRISTOL-MYERS SQUIBB AB 
Tel: + 46 8 704 71 00 
 

Latvija 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Tel: + 371 67 50 21 85 
 

United Kingdom 
BRISTOL-MYERS SQUIBB PHARMACEUTICALS LTD
Tel: + 44 (0800) 731 1736 
 
 

Lietuva 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Tel: + 370 5 2790 762 
 

 

 

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

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PACKAGE LEAFLET: INFORMATION FOR THE USER 
Irbesartan BMS 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 Irbesartan BMS is and what it is used for 
2. Before you take Irbesartan BMS 
3. How to take Irbesartan BMS 
4. Possible side effects 
5. How to store Irbesartan BMS 
6. Further information 
 
 
1. WHAT IRBESARTAN BMS IS AND WHAT IT IS USED FOR 
 
Irbesartan BMS 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. Irbesartan BMS prevents the binding of 
angiotensin-II to these receptors, causing the blood vessels to relax and the blood pressure to lower. 
Irbesartan BMS slows the decrease of kidney function in patients with high blood pressure and type 2 
diabetes. 
 
Irbesartan BMS is used 
 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 IRBESARTAN BMS 
 
Do not take Irbesartan BMS 
 if you are allergic (hypersensitive) to irbesartan or any other ingredients of Irbesartan BMS 
 if you are more than 3 months pregnant. (It is also better to avoid Irbesartan BMS in early 

pregnancy – see pregnancy section) 
 
Irbesartan BMS should not be given to children and adolescents (under 18 years). 
 
Take special care with Irbesartan BMS 
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 Irbesartan BMS 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 
You must tell your doctor if you think you are (or might become) pregnant. Irbesartan BMS 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). 

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Using other medicines 
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, 
including medicines obtained without a prescription. 
 
Irbesartan BMS does not usually interact with other medicines. 
 
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 Irbesartan BMS with food and drink 
Irbesartan BMS 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 Irbesartan BMS before you become pregnant or as soon as you know you are 
pregnant and will advise you to take another medicine instead of Irbesartan BMS. Irbesartan BMS 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. Irbesartan BMS 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. Irbesartan 
BMS 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 Irbesartan BMS 
Irbesartan BMS 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. 
 
 
3. HOW TO TAKE IRBESARTAN BMS 
 
Always take Irbesartan BMS exactly as your doctor has told you. You should check with your doctor 
or pharmacist if you are not sure. 
 
Method of administration 
Irbesartan BMS is for oral use. Swallow the tablets with a sufficient amount of fluid (e.g. one glass of 
water). You can take Irbesartan BMS 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 Irbesartan BMS until your doctor tells 
you otherwise. 
 
 Patients with high blood pressure 

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

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

In patients with high blood pressure and type 2 diabetes, 300 mg (four tablets a day) 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 Irbesartan BMS than you should: 
If you accidentally take too many tablets, contact your doctor immediately. 
 
Children should not take Irbesartan BMS 
Irbesartan BMS 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 Irbesartan BMS: 
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, Irbesartan BMS 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 Irbesartan BMS 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 BMS 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 undesirable effects have been reported since marketing of Irbesartan BMS but the frequency for 
them to occur is not known. These undesirable effects are: headache, taste disturbance, ringing in the 
ears, muscle cramps, pain in joints and muscles, abnormal liver function, increased blood potassium 

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levels, impaired kidney function, and inflammation of small blood vessels mainly affecting the skin (a 
condition known as leukocytoclastic vasculitis). 
 
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 IRBESARTAN BMS 
 
Keep out of the reach and sight of children. 
 
Do not use Irbesartan BMS 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. 
 
Do not store above 30°C. 
 
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 Irbesartan BMS contains 
 The active substance is irbesartan. Each tablet of Irbesartan BMS 75 mg contains 75 mg 

irbesartan. 
 The other ingredients are lactose monohydrate, microcrystalline cellulose, croscarmellose 

sodium, hypromellose, silicon dioxide, magnesium stearate, titanium dioxide, macrogol 3000, 
carnauba wax. 

 
What Irbesartan BMS looks like and contents of the pack 
Irbesartan BMS 75 mg film-coated tablets are white to off-white, biconvex, and oval-shaped with a 
heart debossed on one side and the number 2871 engraved on the other side. 
 
Irbesartan BMS 75 mg film-coated tablets are supplied in blister packs of 14, 28, 56, 84 or 98 film-
coated tablets. Unidose blister packs of 56 x 1 film-coated tablet for delivery in hospitals are also 
available. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder: 
BRISTOL-MYERS SQUIBB PHARMA EEIG 
Uxbridge Business Park 
Sanderson Road 
Uxbridge UB8 1DH - United Kingdom 
 
Manufacturer: 
SANOFI WINTHROP INDUSTRIE 
1, rue de la Vierge 
Ambarès & Lagrave 
F-33565 Carbon Blanc Cedex - France 
 
SANOFI SYNTHELABO LIMITED 
Edgefield Avenue - Fawdon 
Newcastle Upon Tyne, Tyne & Wear NE3 3TT - United Kingdom 
 

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SANOFI WINTHROP INDUSTRIE 
30-36 Avenue Gustave Eiffel, BP 7166 
F-37071 Tours Cedex 2 - France 

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For any information about this medicinal product, please contact the local representative of the 
Marketing Authorisation Holder. 
 
Belgique/België/Belgien 
BRISTOL-MYERS SQUIBB BELGIUM S.A./N.V. 
Tél/Tel: + 32 2 352 74 60 
 

Luxembourg/Luxemburg 
BRISTOL-MYERS SQUIBB BELGIUM S.A./N.V. 
Tél/Tel: + 32 2 352 74 60 
 

България 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Teл.: + 359 800 12 400 
 

Magyarország 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Tel.: + 36 1 301 9700 
 

Česká republika 
BRISTOL-MYERS SQUIBB SPOL. S R.O. 
Tel: + 420 221 016 111 
 

Malta 
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 
 

Danmark 
BRISTOL-MYERS SQUIBB 
Tlf: + 45 45 93 05 06 
 

Nederland 
BRISTOL-MYERS SQUIBB BV 
Tel: + 31 34 857 42 22 
 

Deutschland 
BRISTOL-MYERS SQUIBB GMBH & CO. KGAA 
Tel: + 49 89 121 42-0 
 

Norge 
BRISTOL-MYERS SQUIBB NORWAY LTD 
Tlf: + 47 67 55 53 50 
 

Eesti 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Tel: + 372 640 1301 
 

Österreich 
BRISTOL-MYERS SQUIBB GESMBH 
Tel: + 43 1 60 14 30 
 
 

Ελλάδα 
BRISTOL-MYERS SQUIBB A.E. 
Τηλ: + 30 210 6074300 
 

Polska 
BRISTOL-MYERS SQUIBB POLSKA SP. Z O.O. 
Tel.: + 48 22 5796666 
 

España 
BRISTOL-MYERS SQUIBB, S.A. 
Tel: + 34 91 456 53 00 
 
 

Portugal 
BRISTOL-MYERS SQUIBB FARMACÊUTICA 
PORTUGUESA, S.A. 
Tel: + 351 21 440 70 00 
 

France 
BRISTOL-MYERS SQUIBB SARL 
Tél: + 33 (0)810 410 500 
 
 

România 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Tel: + 40 (0)21 272 16 00 
 

Ireland 
BRISTOL-MYERS SQUIBB PHARMACEUTICALS LTD
Tel: + 353 (1 800) 749 749 
 

Slovenija 
BRISTOL-MYERS SQUIBB SPOL. S R.O. 
Tel: + 386 1 236 47 00 
 

Ísland 
VISTOR HF 
Sími: + 354 535 7000 
 

Slovenská republika 
BRISTOL-MYERS SQUIBB SPOL. S R.O. 
Tel: + 421 2 59298411  
 

Italia 
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 
 

Suomi/Finland 
OY BRISTOL-MYERS SQUIBB (FINLAND) AB 
Puh/Tel: + 358 9 251 21 230 
 

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Κύπρος 
ΑΚΗΣ ΠΑΝΑΓΙΩΤΟΥ & ΥΙΟΣ Ε.Π.Ε. 
Τηλ: + 357 22 677038 
 

Sverige 
BRISTOL-MYERS SQUIBB AB 
Tel: + 46 8 704 71 00 
 

Latvija 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Tel: + 371 67 50 21 85 
 

United Kingdom 
BRISTOL-MYERS SQUIBB PHARMACEUTICALS LTD
Tel: + 44 (0800) 731 1736 
 
 

Lietuva 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Tel: + 370 5 2790 762 
 

 

 

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

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PACKAGE LEAFLET: INFORMATION FOR THE USER 
Irbesartan BMS 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 Irbesartan BMS is and what it is used for 
2. Before you take Irbesartan BMS 
3. How to take Irbesartan BMS 
4. Possible side effects 
5. How to store Irbesartan BMS 
6. Further information 
 
 
1. WHAT IRBESARTAN BMS IS AND WHAT IT IS USED FOR 
 
Irbesartan BMS 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. Irbesartan BMS prevents the binding of 
angiotensin-II to these receptors, causing the blood vessels to relax and the blood pressure to lower. 
Irbesartan BMS slows the decrease of kidney function in patients with high blood pressure and type 2 
diabetes. 
 
Irbesartan BMS is used 
 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 IRBESARTAN BMS 
 
Do not take Irbesartan BMS 
 if you are allergic (hypersensitive) to irbesartan or any other ingredients of Irbesartan BMS 
 if you are more than 3 months pregnant. (It is also better to avoid Irbesartan BMS in early 

pregnancy – see pregnancy section) 
 
Irbesartan BMS should not be given to children and adolescents (under 18 years). 
 
Take special care with Irbesartan BMS 
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 Irbesartan BMS 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 
You must tell your doctor if you think you are (or might become) pregnant. Irbesartan BMS 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). 

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Using other medicines 
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, 
including medicines obtained without a prescription. 
 
Irbesartan BMS does not usually interact with other medicines. 
 
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 Irbesartan BMS with food and drink 
Irbesartan BMS 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 Irbesartan BMS before you become pregnant or as soon as you know you are 
pregnant and will advise you to take another medicine instead of Irbesartan BMS. Irbesartan BMS 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. Irbesartan BMS 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. Irbesartan 
BMS 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 Irbesartan BMS 
Irbesartan BMS 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. 
 
 
3. HOW TO TAKE IRBESARTAN BMS 
 
Always take Irbesartan BMS exactly as your doctor has told you. You should check with your doctor 
or pharmacist if you are not sure. 
 
Method of administration 
Irbesartan BMS is for oral use. Swallow the tablets with a sufficient amount of fluid (e.g. one glass of 
water). You can take Irbesartan BMS 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 Irbesartan BMS 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 (two tablets a 
day) once daily depending on blood pressure response. 

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

In patients with high blood pressure and type 2 diabetes, 300 mg (two tablets a day) 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 Irbesartan BMS than you should: 
If you accidentally take too many tablets, contact your doctor immediately. 
 
Children should not take Irbesartan BMS 
Irbesartan BMS 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 Irbesartan BMS: 
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, Irbesartan BMS 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 Irbesartan BMS 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 BMS 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 undesirable effects have been reported since marketing of Irbesartan BMS but the frequency for 
them to occur is not known. These undesirable effects are: headache, taste disturbance, ringing in the 
ears, muscle cramps, pain in joints and muscles, abnormal liver function, increased blood potassium 

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levels, impaired kidney function, and inflammation of small blood vessels mainly affecting the skin (a 
condition known as leukocytoclastic vasculitis). 
 
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 IRBESARTAN BMS 
 
Keep out of the reach and sight of children. 
 
Do not use Irbesartan BMS 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. 
 
Do not store above 30°C. 
 
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 Irbesartan BMS contains 
 The active substance is irbesartan. Each tablet of Irbesartan BMS 150 mg contains 150 mg 

irbesartan. 
 The other ingredients are lactose monohydrate, microcrystalline cellulose, croscarmellose 

sodium, hypromellose, silicon dioxide, magnesium stearate, titanium dioxide, macrogol 3000, 
carnauba wax. 

 
What Irbesartan BMS looks like and contents of the pack 
Irbesartan BMS 150 mg film-coated tablets are white to off-white, biconvex, and oval-shaped with a 
heart debossed on one side and the number 2872 engraved on the other side. 
 
Irbesartan BMS 150 mg film-coated tablets are supplied in blister packs of 14, 28, 56, 84 or 98 film-
coated tablets. Unidose blister packs of 56 x 1 film-coated tablet for delivery in hospitals are also 
available. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder: 
BRISTOL-MYERS SQUIBB PHARMA EEIG 
Uxbridge Business Park 
Sanderson Road 
Uxbridge UB8 1DH - United Kingdom 
 
Manufacturer: 
SANOFI WINTHROP INDUSTRIE 
1, rue de la Vierge 
Ambarès & Lagrave 
F-33565 Carbon Blanc Cedex - France 
 
SANOFI SYNTHELABO LIMITED 
Edgefield Avenue - Fawdon 
Newcastle Upon Tyne, Tyne & Wear NE3 3TT - United Kingdom 
 

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SANOFI WINTHROP INDUSTRIE 
30-36 Avenue Gustave Eiffel, BP 7166 
F-37071 Tours Cedex 2 - France 
 
CHINOIN PRIVATE CO. LTD. 
Lévai u.5. 
2112 Veresegyház - Hungary 

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For any information about this medicinal product, please contact the local representative of the 
Marketing Authorisation Holder. 
 
Belgique/België/Belgien 
BRISTOL-MYERS SQUIBB BELGIUM S.A./N.V. 
Tél/Tel: + 32 2 352 74 60 
 

Luxembourg/Luxemburg 
BRISTOL-MYERS SQUIBB BELGIUM S.A./N.V. 
Tél/Tel: + 32 2 352 74 60 
 

България 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Teл.: + 359 800 12 400 
 

Magyarország 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Tel.: + 36 1 301 9700 
 

Česká republika 
BRISTOL-MYERS SQUIBB SPOL. S R.O. 
Tel: + 420 221 016 111 
 

Malta 
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 
 

Danmark 
BRISTOL-MYERS SQUIBB 
Tlf: + 45 45 93 05 06 
 

Nederland 
BRISTOL-MYERS SQUIBB BV 
Tel: + 31 34 857 42 22 
 

Deutschland 
BRISTOL-MYERS SQUIBB GMBH & CO. KGAA 
Tel: + 49 89 121 42-0 
 

Norge 
BRISTOL-MYERS SQUIBB NORWAY LTD 
Tlf: + 47 67 55 53 50 
 

Eesti 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Tel: + 372 640 1301 
 

Österreich 
BRISTOL-MYERS SQUIBB GESMBH 
Tel: + 43 1 60 14 30 
 
 

Ελλάδα 
BRISTOL-MYERS SQUIBB A.E. 
Τηλ: + 30 210 6074300 
 

Polska 
BRISTOL-MYERS SQUIBB POLSKA SP. Z O.O. 
Tel.: + 48 22 5796666 
 

España 
BRISTOL-MYERS SQUIBB, S.A. 
Tel: + 34 91 456 53 00 
 
 

Portugal 
BRISTOL-MYERS SQUIBB FARMACÊUTICA 
PORTUGUESA, S.A. 
Tel: + 351 21 440 70 00 
 

France 
BRISTOL-MYERS SQUIBB SARL 
Tél: + 33 (0)810 410 500 
 
 

România 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Tel: + 40 (0)21 272 16 00 
 

Ireland 
BRISTOL-MYERS SQUIBB PHARMACEUTICALS LTD
Tel: + 353 (1 800) 749 749 
 

Slovenija 
BRISTOL-MYERS SQUIBB SPOL. S R.O. 
Tel: + 386 1 236 47 00 
 

Ísland 
VISTOR HF 
Sími: + 354 535 7000 
 

Slovenská republika 
BRISTOL-MYERS SQUIBB SPOL. S R.O. 
Tel: + 421 2 59298411  
 

Italia 
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 
 

Suomi/Finland 
OY BRISTOL-MYERS SQUIBB (FINLAND) AB 
Puh/Tel: + 358 9 251 21 230 
 

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Κύπρος 
ΑΚΗΣ ΠΑΝΑΓΙΩΤΟΥ & ΥΙΟΣ Ε.Π.Ε. 
Τηλ: + 357 22 677038 
 

Sverige 
BRISTOL-MYERS SQUIBB AB 
Tel: + 46 8 704 71 00 
 

Latvija 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Tel: + 371 67 50 21 85 
 

United Kingdom 
BRISTOL-MYERS SQUIBB PHARMACEUTICALS LTD
Tel: + 44 (0800) 731 1736 
 
 

Lietuva 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Tel: + 370 5 2790 762 
 

 

 

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

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PACKAGE LEAFLET: INFORMATION FOR THE USER 
Irbesartan BMS 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 Irbesartan BMS is and what it is used for 
2. Before you take Irbesartan BMS 
3. How to take Irbesartan BMS 
4. Possible side effects 
5. How to store Irbesartan BMS 
6. Further information 
 
 
1. WHAT IRBESARTAN BMS IS AND WHAT IT IS USED FOR 
 
Irbesartan BMS 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. Irbesartan BMS prevents the binding of 
angiotensin-II to these receptors, causing the blood vessels to relax and the blood pressure to lower. 
Irbesartan BMS slows the decrease of kidney function in patients with high blood pressure and type 2 
diabetes. 
 
Irbesartan BMS is used 
 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 IRBESARTAN BMS 
 
Do not take Irbesartan BMS 
 if you are allergic (hypersensitive) to irbesartan or any other ingredients of Irbesartan BMS 
 if you are more than 3 months pregnant. (It is also better to avoid Irbesartan BMS in early 

pregnancy – see pregnancy section) 
 
Irbesartan BMS should not be given to children and adolescents (under 18 years). 
 
Take special care with Irbesartan BMS 
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 Irbesartan BMS 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 
You must tell your doctor if you think you are (or might become) pregnant. Irbesartan BMS 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). 

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Using other medicines 
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, 
including medicines obtained without a prescription. 
 
Irbesartan BMS does not usually interact with other medicines. 
 
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 Irbesartan BMS with food and drink 
Irbesartan BMS 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 Irbesartan BMS before you become pregnant or as soon as you know you are 
pregnant and will advise you to take another medicine instead of Irbesartan BMS. Irbesartan BMS 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. Irbesartan BMS 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. Irbesartan 
BMS 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 Irbesartan BMS 
Irbesartan BMS 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. 
 
 
3. HOW TO TAKE IRBESARTAN BMS 
 
Always take Irbesartan BMS exactly as your doctor has told you. You should check with your doctor 
or pharmacist if you are not sure. 
 
Method of administration 
Irbesartan BMS is for oral use. Swallow the tablets with a sufficient amount of fluid (e.g. one glass of 
water). You can take Irbesartan BMS 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 Irbesartan BMS 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. 

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 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 Irbesartan BMS than you should: 
If you accidentally take too many tablets, contact your doctor immediately. 
 
Children should not take Irbesartan BMS 
Irbesartan BMS 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 Irbesartan BMS: 
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, Irbesartan BMS 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 Irbesartan BMS 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 BMS 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 undesirable effects have been reported since marketing of Irbesartan BMS but the frequency for 
them to occur is not known. These undesirable effects are: headache, taste disturbance, ringing in the 
ears, muscle cramps, pain in joints and muscles, abnormal liver function, increased blood potassium 

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levels, impaired kidney function, and inflammation of small blood vessels mainly affecting the skin (a 
condition known as leukocytoclastic vasculitis). 
 
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 IRBESARTAN BMS 
 
Keep out of the reach and sight of children. 
 
Do not use Irbesartan BMS 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. 
 
Do not store above 30°C. 
 
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 Irbesartan BMS contains 
 The active substance is irbesartan. Each tablet of Irbesartan BMS 300 mg contains 300 mg 

irbesartan. 
 The other ingredients are lactose monohydrate, microcrystalline cellulose, croscarmellose 

sodium, hypromellose, silicon dioxide, magnesium stearate, titanium dioxide, macrogol 3000, 
carnauba wax. 

 
What Irbesartan BMS looks like and contents of the pack 
Irbesartan BMS 300 mg film-coated tablets are white to off-white, biconvex, and oval-shaped with a 
heart debossed on one side and the number 2873 engraved on the other side. 
 
Irbesartan BMS 300 mg film-coated tablets are supplied in blister packs of 14, 28, 56, 84 or 98 film-
coated tablets. Unidose blister packs of 56 x 1 film-coated tablet for delivery in hospitals are also 
available. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder: 
BRISTOL-MYERS SQUIBB PHARMA EEIG 
Uxbridge Business Park 
Sanderson Road 
Uxbridge UB8 1DH - United Kingdom 
 
Manufacturer: 
SANOFI WINTHROP INDUSTRIE 
1, rue de la Vierge 
Ambarès & Lagrave 
F-33565 Carbon Blanc Cedex - France 
 
SANOFI SYNTHELABO LIMITED 
Edgefield Avenue - Fawdon 
Newcastle Upon Tyne, Tyne & Wear NE3 3TT - United Kingdom 
 

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SANOFI WINTHROP INDUSTRIE 
30-36 Avenue Gustave Eiffel, BP 7166 
F-37071 Tours Cedex 2 - France 
 
CHINOIN PRIVATE CO. LTD. 
Lévai u.5. 
2112 Veresegyház - Hungary 

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For any information about this medicinal product, please contact the local representative of the 
Marketing Authorisation Holder. 
 
Belgique/België/Belgien 
BRISTOL-MYERS SQUIBB BELGIUM S.A./N.V. 
Tél/Tel: + 32 2 352 74 60 
 

Luxembourg/Luxemburg 
BRISTOL-MYERS SQUIBB BELGIUM S.A./N.V. 
Tél/Tel: + 32 2 352 74 60 
 

България 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Teл.: + 359 800 12 400 
 

Magyarország 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Tel.: + 36 1 301 9700 
 

Česká republika 
BRISTOL-MYERS SQUIBB SPOL. S R.O. 
Tel: + 420 221 016 111 
 

Malta 
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 
 

Danmark 
BRISTOL-MYERS SQUIBB 
Tlf: + 45 45 93 05 06 
 

Nederland 
BRISTOL-MYERS SQUIBB BV 
Tel: + 31 34 857 42 22 
 

Deutschland 
BRISTOL-MYERS SQUIBB GMBH & CO. KGAA 
Tel: + 49 89 121 42-0 
 

Norge 
BRISTOL-MYERS SQUIBB NORWAY LTD 
Tlf: + 47 67 55 53 50 
 

Eesti 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Tel: + 372 640 1301 
 

Österreich 
BRISTOL-MYERS SQUIBB GESMBH 
Tel: + 43 1 60 14 30 
 
 

Ελλάδα 
BRISTOL-MYERS SQUIBB A.E. 
Τηλ: + 30 210 6074300 
 

Polska 
BRISTOL-MYERS SQUIBB POLSKA SP. Z O.O. 
Tel.: + 48 22 5796666 
 

España 
BRISTOL-MYERS SQUIBB, S.A. 
Tel: + 34 91 456 53 00 
 
 

Portugal 
BRISTOL-MYERS SQUIBB FARMACÊUTICA 
PORTUGUESA, S.A. 
Tel: + 351 21 440 70 00 
 

France 
BRISTOL-MYERS SQUIBB SARL 
Tél: + 33 (0)810 410 500 
 
 

România 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Tel: + 40 (0)21 272 16 00 
 

Ireland 
BRISTOL-MYERS SQUIBB PHARMACEUTICALS LTD
Tel: + 353 (1 800) 749 749 
 

Slovenija 
BRISTOL-MYERS SQUIBB SPOL. S R.O. 
Tel: + 386 1 236 47 00 
 

Ísland 
VISTOR HF 
Sími: + 354 535 7000 
 

Slovenská republika 
BRISTOL-MYERS SQUIBB SPOL. S R.O. 
Tel: + 421 2 59298411  
 

Italia 
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 
 

Suomi/Finland 
OY BRISTOL-MYERS SQUIBB (FINLAND) AB 
Puh/Tel: + 358 9 251 21 230 
 

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Κύπρος 
ΑΚΗΣ ΠΑΝΑΓΙΩΤΟΥ & ΥΙΟΣ Ε.Π.Ε. 
Τηλ: + 357 22 677038 
 

Sverige 
BRISTOL-MYERS SQUIBB AB 
Tel: + 46 8 704 71 00 
 

Latvija 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Tel: + 371 67 50 21 85 
 

United Kingdom 
BRISTOL-MYERS SQUIBB PHARMACEUTICALS LTD
Tel: + 44 (0800) 731 1736 
 
 

Lietuva 
BRISTOL-MYERS SQUIBB 
GYÓGYSZERKERESKEDELMI KFT. 
Tel: + 370 5 2790 762 
 

 

 

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

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	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURING AUTHORISATION HOLDERS RESPONSIBLE FOR BATCHRELEASE
	B. CONDITIONS OF THE MARKETING AUTHORISATION
	A. LABELLING
	B. PACKAGE LEAFLET