Tolura

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS



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1. NAME OF THE MEDICINAL PRODUCT

Tolura 20 mg tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 20 mg telmisartan.

Excipients with known effect:
Each tablet contains 74.9 mg sorbitol (E420) and 28.5 mg lactose.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Tablet.

20 mg: white to almost white, round tablets

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Hypertension
Treatment of essential hypertension in adults.

Cardiovascular prevention
Reduction of cardiovascular morbidity in adults with:
- manifest atherothrombotic cardiovascular disease (history of coronary heart disease, stroke, or 

peripheral arterial disease) or
- type 2 diabetes mellitus with documented target organ damage.

4.2 Posology and method of administration

Posology

Treatment of essential hypertension:

The usually effective dose is 40 mg once daily. Some patients may already benefit at a daily dose of 
20 mg. In cases where the target blood pressure is not achieved, the dose of telmisartan can be 
increased to a maximum of 80 mg once daily. Alternatively, telmisartan may be used in combination 
with thiazide-type diuretics such as hydrochlorothiazide, which has been shown to have an additive 
blood pressure lowering effect with telmisartan. When considering raising the dose, it must be borne 
in mind that the maximum antihypertensive effect is generally attained four to eight weeks after the 
start of treatment (see section 5.1).

Cardiovascular prevention:

The recommended dose is 80 mg once daily. It is not known whether doses lower than 80 mg of 
telmisartan are effective in reducing cardiovascular morbidity.
When initiating telmisartan therapy for the reduction of cardiovascular morbidity, close monitoring of 
blood pressure is recommended, and if appropriate adjustment of medications that lower blood 
pressure may be necessary.



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Special populations

Patients with renal impairment

Limited experience is available in patients with severe renal impairment or haemodialysis. A lower 
starting dose of 20 mg is recommended in these patients (see section 4.4). No posology adjustment is 
required for patients with mild to moderate renal impairment.

Patients with hepatic impairment

Tolura is contraindicated in patients with severe hepatic impairment (see section 4.3).
In patients with mild to moderate hepatic impairment the posology should not exceed 40 mg once 
daily (see section 4.4).

Elderly patients
No dose adjustment is necessary for elderly patients.

Paediatric population

The safety and efficacy of Tolura in children and adolescents aged below 18 years have not been 
established.
Currently available data are described in section 5.1 and 5.2 but no recommendation on a posology can 
be made.

Method of administration

Telmisartan tablets are for once-daily oral administration and should be taken with liquid, with or 
without food.

Precautions to be taken before handling or administering the medicinal product

Telmisartan should be kept in the sealed blister due to the hygroscopic property of the tablets. Tablets 
should be taken out of the blister shortly before administration (see section 6.6).

4.3 Contraindications

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1
- Second and third trimester of pregnancy (see sections 4.4 and 4.6)
- Biliary obstructive disorders
- Severe hepatic impairment

The concomitant use of Tolura with aliskiren-containing products is contraindicated in patients with 
diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m2) (see sections 4.5 and 5.1).

4.4 Special warnings and precautions for use

Pregnancy

Angiotensin II receptor antagonists should not be initiated during pregnancy. Unless continued 
angiotensin II receptor antagonist 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 angiotensin II receptor antagonists should 
be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 
4.6).

Hepatic impairment



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Tolura is not to be given to patients with cholestasis, biliary obstructive disorders or severe hepatic 
impairment (see section 4.3) since telmisartan is mostly eliminated with the bile. These patients can be 
expected to have reduced hepatic clearance for telmisartan. Tolura should be used only with caution in 
patients with mild to moderate hepatic impairment.

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.

Renal impairment and kidney transplantation

When Tolura is used in patients with impaired renal function, periodic monitoring of potassium and 
creatinine serum levels is recommended. There is no experience regarding the administration of Tolura
in patients with recent kidney transplantation.

Intravascular hypovolaemia

Symptomatic hypotension, especially after the first dose of Tolura, 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 Tolura. Volume and/or 
sodium depletion should be corrected prior to administration of Tolura.

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

There is evidence that the concomitant use of ACE-inhibitors, angiotensin II receptor blockers or 
aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including 
acute renal failure). Dual blockade of RAAS through the combined use of ACE-inhibitors, angiotensin 
II receptor blockers or aliskiren is therefore not recommended (see sections 4.5 and 5.1).
If dual blockade therapy is considered absolutely necessary, this should only occur under specialist 
supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure.
ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with 
diabetic nephropathy.

Other conditions with stimulation of the renin-angiotensin-aldosterone system

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 medicinal products that affect this system such 
as telmisartan has been associated with acute hypotension, hyperazotaemia, oliguria, or rarely acute 
renal failure (see section 4.8).

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 telmisartan is not 
recommended.

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.

Diabetic patients treated with insulin or antidiabetics

In these patients hypoglycaemia may occur under telmisartan treatment. Therefore, in these patients an 



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approptiate blood glucose monitoring should be considered; a dose adjustment of insulin or 
antidiabetics may be required, when indicated.

Hyperkalaemia

The use of medicinal products that affect the renin-angiotensin-aldosterone system may cause 
hyperkalaemia.

In the elderly, in patients with renal insufficiency, in diabetic patients, in patients concomitantly 
treated with other medicinal products that may increase potassium levels, and/or in patients with 
intercurrent events, hyperkalaemia may be fatal.

Before considering the concomitant use of medicinal products that affect the renin-angiotensin-
aldosterone system, the benefit risk ratio should be evaluated.

The main risk factors for hyperkalaemia to be considered are:
- Diabetes mellitus, renal impairment, age (>70 years).
- Combination with one or more other medicinal products that affect the renin-angiotensin-

aldosterone system and/or potassium supplements. Medicinal products or therapeutic classes of 
medicinal products that may provoke hyperkalaemia are salt substitutes containing potassium, 
potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, non steroidal 
anti-inflammatory medicinal products (NSAIDs, including selective COX-2 inhibitors), heparin, 
immunosuppressives (cyclosporin or tacrolimus), and trimethoprim.

- Intercurrent events, in particular dehydratation, acute cardiac decompensation, metabolic 
acidosis, worsening of renal function, sudden worsening of the renal condition (e.g. infectious 
diseases), cellular lysis (e.g. acute limb ischemia, rhabdomyolysis, extend trauma).

Close monitoring of serum potassium in at risk patients is recommended (see section 4.5).

Sorbitol

Tolura tablets contain sorbitol (E420). Patients with rare hereditary problems of fructose intolerance 
should not take Tolura.

Lactose

Tolura tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the 
Lapp lactase deficiency or glucose-galactose malabsorption should not take Tolura.

Ethnic differences

As observed for angiotensin converting enzyme inhibitors, telmisartan and the other angiotensin II 
receptor 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.

Other

As with any antihypertensive agent, excessive reduction of blood pressure in patients with ischaemic 
cardiopathy or ischaemic cardiovascular disease could result in a myocardial infarction or stroke.

4.5 Interaction with other medicinal products and other forms of interaction

Digoxin

When telmisartan was co-administered with digoxin, median increases in digoxin peak plasma 
concentration (49%) and in trough concentration (20%) were observed. When initiating, adjusting, and 



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discontinuing telmisartan, monitor digoxin levels in order to maintain levels within the therapeutic 
range.

As with other medicinal products acting on the renin-angiotensin-aldosterone system, telmisartan may 
provoke hyperkalaemia (see section 4.4). The risk may increase in case of treatment combination with 
other medicinal products that may also provoke hyperkalaemia (salt substitutes containing potassium, 
potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, non steroidal anti-
inflammatory medicinal products (NSAIDs, including selective COX-2 inhibitors), heparin, 
immunosuppressives (cyclosporin or tacrolimus), and trimethoprim).

The occurrence of hyperkalaemia depends on associated risk factors. The risk is increased in case of 
the above-mentioned treatment combinations. The risk is particularly high in combination with 
potassium sparing-diuretics, and when combined with salt substitutes containing potassium. A 
combination with ACE inhibitors or NSAIDs, for example, presents a lesser risk provided that 
precautions for use are strictly followed.

Concomitant use not recommended

Potassium sparing diuretics or potassium supplements

Angiotensin II receptor antagonists such as telmisartan, attenuate diuretic induced potassium loss. 
Potassium sparing diuretics e.g. spirinolactone, eplerenone, triamterene, or amiloride, potassium 
supplements, or potassium-containing salt substitutes may lead to a significant increase in serum 
potassium. If concomitant use is indicated because of documented hypokalaemia they should be used 
with caution and with frequent monitoring of serum potassium.

Lithium

Reversible increases in serum lithium concentrations and toxicity have been reported during 
concomitant administration of lithium with angiotensin converting enzyme inhibitors, and with 
angiotensin II receptor antagonists, including telmisartan. If use of the combination proves necessary, 
careful monitoring of serum lithium levels is recommended.

Concomitant use requiring caution

Non-steroidal anti-inflammatory medicinal products

NSAIDs (i.e. acetylsalicylic acid at anti-inflammatory dosage regimens, COX-2 inhibitors and non-
selective NSAIDs) may reduce the antihypertensive effect of angiotensin II receptor antagonists.
In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with 
compromised renal function), the co-administration of angiotensin II receptor antagonists and agents 
that inhibit cyclo-oxygenase may result in further deterioration of renal function, including possible 
acute renal failure, which is usually reversible. Therefore, the combination should be administered 
with caution, especially in the elderly. Patients should be adequately hydrated and consideration 
should be given to monitoring of renal function after initiation of concomitant therapy and periodically 
thereafter.

In one study the co-administration of telmisartan and ramipril led to an increase of up to 2.5 fold in the 
AUC0-24 and Cmax of ramipril and ramiprilat. The clinical relevance of this observation is not known.

Diuretics (thiazide or loop diuretics)

Prior treatment with high dose diuretics such as furosemide (loop diuretic) and hydrochlorothiazide 
(thiazide diuretic) may result in volume depletion and in a risk of hypotension when initiating therapy 
with telmisartan.

To be taken into account with concomitant use



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Other antihypertensive agents

The blood pressure lowering effect of telmisartan can be increased by concomitant use of other 
antihypertensive medicinal products.

Clinical trial data has shown that dual blockade of the renin-angiotensin-aldosterone-system (RAAS) 
through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is associated 
with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal 
function (including acute renal failure) compared to the use of a single RAAS-acting agent (see 
sections 4.3, 4.4 and 5.1).

Based on their pharmacological properties it can be expected that the following medicinal products 
may potentiate the hypotensive effects of all antihypertensives including telmisartan: Baclofen, 
amifostine. Furthermore, orthostatic hypotension may be aggravated by alcohol, barbiturates, narcotics 
or antidepressants.

Corticosteroids (systemic route)

Reduction of the antihypertensive effect.

4.6 Fertility, pregnancy and lactation

Pregnancy

The use of angiotensin II receptor antagonists is not recommended during the first trimester of 
pregnancy (see section 4.4). The use of angiotensin II receptor antagonists is contraindicated during 
the second and third trimesters of pregnancy (see sections 4.3 and 4.4).

There are no adequate data from the use of Tolura in pregnant women. Studies in animals have shown 
reproductive toxicity (see section 5.3).

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, similar risks may exist for this class of drugs. Unless continued angiotensin II 
receptor antagonist 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 angiotensin II receptor antagonists should be stopped 
immediately, and, if appropriate, alternative therapy should be started.

Exposure to angiotensin II receptor antagonist 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 angiotensin II receptor antagonists have occurred from the second trimester of 
pregnancy, ultrasound check of renal function and skull is recommended.
Infants whose mothers have taken angiotensin II receptor antagonists should be closely observed for 
hypotension (see sections 4.3 and 4.4).

Breast-feeding

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

Fertility



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In preclinical studies, no effects of Tolura on male and female fertility were observed.

4.7 Effects on ability to drive and use machines

When driving vehicles or operating machinery it should be taken into account that dizziness or 
drowsiness may occasionally occur when taking antihypertensive therapy such as Tolura.

4.8 Undesirable effects

Summary of the safety profile

Serious adverse drug reactions include anaphylactic reaction and angioedema which may occur rarely 
(≥1/10,000 to <1/1,000), and acute renal failure.

The overall incidence of adverse reactions reported with telmisartan was usually comparable to 
placebo (41.4 % vs 43.9 %) in controlled trials in patients treated for hypertension. The incidence of 
adverse reactions was not dose related and showed no correlation with gender, age or race of the 
patients. The safety profile of telmisartan in patients treated for the reduction of cardiovascular 
morbidity was consistent with that obtained in hypertensive patients.

The adverse reactions listed below have been accumulated from controlled clinical trials in patients 
treated for hypertension and from post-marketing reports. The listing also takes into account serious 
adverse reactions and adverse reactions leading to discontinuation reported in three clinical long-term 
studies including 21642 patients treated with telmisartan for the reduction of cardiovascular morbidity 
for up to six years.

Tabulated summary of adverse reactions

Adverse reactions have been ranked under headings of frequency using the following convention:
very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100);
rare (≥1/10,000 to <1/1,000); very rare (<1/10,000).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Infections and infestations 

Uncommon:

Rare: 

Urinary tract infection including cystitis, upper respiratory tract infection 
including pharyngitis and sinusitis
Sepsis including fatal outcome1

Blood and the lymphatic system disorders 
Uncommon:
Rare: 

Anaemia
Eosinophilia, thrombocytopenia

Immune system disorders 
Rare: Anaphylactic reaction, hypersensitivity

Metabolism and nutrition disorders 
Uncommon:
Rare:

Hyperkalaemia
Hypoglycaemia (in diabetic patients)

Psychiatric disorders 
Uncommon:
Rare:

Insomnia, depression
Anxiety

Nervous system disorders 
Uncommon:
Rare:

Syncope
Somnolence



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Eye disorders 
Rare: Visual disturbance

Ear and labyrinth disorders 
Uncommon: Vertigo 

Cardiac disorders 
Uncommon:
Rare: 

Bradycardia
Tachycardia 

Vascular disorders 

Uncommon: Hypotension2, orthostatic hypotension

Respiratory, thoracic and mediastinal disorders 
Uncommon:
Very rare:

Dyspnoea, cough
Interstitial lung disease4

Gastrointestinal disorders 
Uncommon:
Rare: 

Abdominal pain, diarrhoea, dyspepsia, flatulence, vomiting
Dry mouth, stomach discomfort, dysgeusia

Hepato-biliary disorders 
Rare: Hepatic function abnormal/liver disorder3

Skin and subcutaneous tissue disorders 
Uncommon:
Rare:

Pruritus, hyperhidrosis, rash
Angioedema (also with fatal outcome), eczema, erythema, urticaria, drug 
eruption, toxic skin eruption

Muscoloskeletal and connective tissue disorders 
Uncommon:
Rare:

Back pain (e.g. sciatica), muscle spasms, myalgia,
Arthralgia, pain in extremity, tendon pain (tendinitis like symptoms)

Renal and urinary disorders 
Uncommon: Renal impairment including acute renal failure 

General disorders and administration site conditions 
Uncommon: 
Rare:

Chest pain, asthenia (weakness)
Influenza-like illness

Investigations 

Uncommon:
Rare:

Blood creatinine increased
Haemoglobin decreased, blood uric acid increased, hepatic enzyme 
increased, blood creatine phosphokinase increased 

1, 2, 3, 4: for further descriptions, please see sub-section “Description of selected adverse reactions”

Description of selected adverse reactions

Sepsis
In the PRoFESS trial, an increased incidence of sepsis was observed with telmisartan compared with 
placebo. The event may be a chance finding or related to a mechanism currently not known (see also 
section 5.1).

Hypotension



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This adverse reaction was reported as common in patients with controlled blood pressure who were 
treated with telmisartan for the reduction of cardiovascular morbidity on top of standard care.

Hepatic function abnormal/liver disorder
Most cases of hepatic function abnormal/liver disorder from post-marketing experience occurred in 
Japanese patients. Japanese patients are more likely to experience these adverse reactions.

Interstitial lung disease
Cases of interstitial lung disease have been reported from post-marketing experience in temporal 
association with the intake of telmisartan. However, a causal relationship has not been established.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.

4.9 Overdose

There is limited information available with regard to overdose in humans.

Symptoms: The most prominent manifestations of telmisartan overdose were hypotension and 
tachycardia; bradycardia, dizziness, increase in serum creatinine, and acute renal failure have also 
been reported.

Treatment: Telmisartan is not removed by haemodialysis. The patient should be closely monitored, 
and the treatment should be symptomatic and supportive. Management depends on the time since 
ingestion and the severity of the symptoms. Suggested measures include induction of emesis and / or 
gastric lavage. Activated charcoal may be useful in the treatment of overdosage. Serum electrolytes 
and creatinine should be monitored frequently. If hypotension occurs, the patient should be placed in a 
supine position, with salt and volume replacement given quickly.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Angiotensin II Antagonists, plain, ATC code: C09CA07.

Mechanism of action

Telmisartan is an orally active and specific angiotensin II receptor (type AT1) antagonist. Telmisartan 
displaces angiotensin II with very high affinity from its binding site at the AT1 receptor subtype, which 
is responsible for the known actions of angiotensin II. Telmisartan does not exhibit any partial agonist 
activity at the AT1 receptor. Telmisartan selectively binds the AT1 receptor. The binding is long-
lasting. Telmisartan does not show affinity for other receptors, including AT2 and other less 
characterised AT receptors. The functional role of these receptors is not known, nor is the effect of 
their possible overstimulation by angiotensin II, whose levels are increased by telmisartan. Plasma 
aldosterone levels are decreased by telmisartan. Telmisartan does not inhibit human plasma renin or 
block ion channels. Telmisartan does not inhibit angiotensin converting enzyme (kininase II), the 
enzyme which also degrades bradykinin. Therefore it is not expected to potentiate bradykinin-
mediated adverse effects.

In human, an 80 mg dose of telmisartan almost completely inhibits the angiotensin II evoked blood 
pressure increase. The inhibitory effect is maintained over 24 hours and still measurable up to 
48 hours.



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Clinical efficacy and safety

Treatment of essential hypertension
After the first dose of telmisartan, the antihypertensive activity gradually becomes evident within 
3 hours. The maximum reduction in blood pressure is generally attained 4 to 8 weeks after the start of 
treatment and is sustained during long-term therapy.

The antihypertensive effect persists constantly over 24 hours after dosing and includes the last 4 hours 
before the next dose as shown by ambulatory blood pressure measurements. This is confirmed by 
trough to peak ratios consistently above 80 % seen after doses of 40 and 80 mg of telmisartan in 
placebo controlled clinical studies. There is an apparent trend to a dose relationship to a time to 
recovery of baseline systolic blood pressure (SBP). In this respect data concerning diastolic blood 
pressure (DBP) are inconsistent.

In patients with hypertension telmisartan reduces both systolic and diastolic blood pressure without 
affecting pulse rate. The contribution of the medicinal product's diuretic and natriuretic effect to its 
hypotensive activity has still to be defined. The antihypertensive efficacy of telmisartan is comparable 
to that of agents representative of other classes of antihypertensive medicinal products (demonstrated 
in clinical trials comparing telmisartan to amlodipine, atenolol, enalapril, hydrochlorothiazide, and 
lisinopril).

Upon abrupt cessation of treatment with telmisartan, blood pressure gradually returns to pre-treatment 
values over a period of several days without evidence of rebound hypertension.

The incidence of dry cough was significantly lower in patients treated with telmisartan than in those 
given angiotensin converting enzyme inhibitors in clinical trials directly comparing the two 
antihypertensive treatments.

Cardiovascular prevention
ONTARGET (ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial) 
compared the effects of telmisartan, ramipril and the combination of telmisartan and ramipril on 
cardiovascular outcomes in 25620 patients aged 55 years or older with a history of coronary artery 
disease, stroke, TIA, peripheral arterial disease, or type 2 diabetes mellitus accompanied by evidence
of end-organ damage (e.g. retinopathy, left ventricular hypertrophy, macro- or microalbuminuria), 
which is a population at risk for cardiovascular events.

Patients were randomized to one of the three following treatment groups: telmisartan 80 mg (n = 
8542), ramipril 10 mg (n = 8576), or the combination of telmisartan 80 mg plus ramipril 10 mg (n = 
8502), and followed for a mean observation time of 4.5 years.

Telmisartan showed a similar effect to ramipril in reducing the primary composite endpoint of 
cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for 
congestive heart failure. The incidence of the primary endpoint was similar in the telmisartan (16.7 %) 
and ramipril (16.5 %) groups. The hazard ratio for telmisartan vs. ramipril was 1.01 (97.5 % CI 0.93 -
1.10, p (non-inferiority) = 0.0019 at a margin of 1.13). The all-cause mortality rate was 11.6 % and 
11.8 % among telmisartan and ramipril treated patients, respectively.

Telmisartan was found to be similarly effective to ramipril in the pre-specified secondary endpoint of 
cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke [0.99 (97.5 % CI 0.90 -
1.08), p (non-inferiority) = 0.0004], the primary endpoint in the reference study HOPE (The Heart 
Outcomes Prevention Evaluation Study), which had investigated the effect of ramipril vs. placebo.

TRANSCEND randomized ACE-I intolerant patients with otherwise similar inclusion criteria as 
ONTARGET to telmisartan 80 mg (n=2954) or placebo (n=2972), both given on top of standard care. 
The mean duration of follow up was 4 years and 8 months. No statistically significant difference in the 
incidence of the primary composite endpoint (cardiovascular death, non-fatal myocardial infarction, 
non-fatal stroke, or hospitalization for congestive heart failure) was found [15.7 % in the telmisartan 



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and 17.0 % in the placebo groups with a hazard ratio of 0.92 (95 % CI 0.81 - 1.05, p = 0.22)]. There 
was evidence for a benefit of telmisartan compared to placebo in the pre-specified secondary 
composite endpoint of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke 
[0.87 (95 % CI 0.76 - 1.00, p = 0.048)]. There was no evidence for benefit on cardiovascular mortality 
(hazard ratio 1.03, 95 % CI 0.85 - 1.24).

Cough and angioedema were less frequently reported in patients treated with telmisartan than in 
patients treated with ramipril, whereas hypotension was more frequently reported with telmisartan.

Combining telmisartan with ramipril did not add further benefit over ramipril or telmisartan alone. CV 
mortality and all cause mortality were numerically higher with the combination. In addition, there was 
a significantly higher incidence of hyperkalaemia, renal failure, hypotension and syncope in the
combination arm. Therefore the use of a combination of telmisartan and ramipril is not recommended 
in this population.

In the “Prevention Regimen For Effectively avoiding Second Strokes” (PRoFESS) trial in patients 50 
years and older, who recently experienced stroke, an increased incidence of sepsis was noted for 
telmisartan compared with placebo, 0,70 % vs. 0,49 % RR 1,43 (95 % confidence interval 1,00 –
2,06) the incidence of fatal sepsis cases was increased for patients taking telmisartan (0,33 %) vs. 
patients taking placebo (0,16 %) RR 2,07 (95 % confidence interval 1,14 – 3,76). The observed 
increased occurrence rate of sepsis associated with the use of telmisartan may be either a chance 
finding or related to a mechanism not currently known.

Two large randomised, controlled trials (ONTARGET (ONgoing Telmisartan Alone and in 
combination with Ramipril Global Endpoint Trial) and VA NEPHRON-D (The Veterans Affairs 
Nephropathy in Diabetes)) have examined the use of the combination of an ACE-inhibitor with an 
angiotensin II receptor blocker.
ONTARGET was a study conducted in patients with a history of cardiovascular or cerebrovascular 
disease, or type 2 diabetes mellitus accompanied by evidence of end-organ damage. VA NEPHRON-D 
was a study in patients with type 2 diabetes mellitus and diabetic nephropathy.
These studies have shown no significant beneficial effect on renal and/or cardiovascular outcomes and 
mortality, while an increased risk of hyperkalaemia, acute kidney injury and/or hypotension as 
compared to monotherapy was observed. Given their similar pharmacodynamic properties, these 
results are also relevant for other ACE-inhibitors and angiotensin II receptor blockers.
ACE-inhibitors and angiotensin II receptor blockers should therefore not be used concomitantly in 
patients with diabetic nephropathy.
ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) 
was a study designed to test the benefit of adding aliskiren to a standard therapy of an ACE-inhibitor 
or an angiotensin II receptor blocker in patients with type 2 diabetes mellitus and chronic kidney 
disease, cardiovascular disease, or both. The study was terminated early because of an increased risk 
of adverse outcomes. Cardiovascular death and stroke were both numerically more frequent in the 
aliskiren group than in the placebo group and adverse events and serious adverse events of interest 
(hyperkalaemia, hypotension and renal dysfunction) were more frequently reported in the aliskiren 
group than in the placebo group.

Paediatric population

The safety and efficacy of telmisartan in children and adolescents aged below 18 years have not been 
established.

The blood pressure lowering effects of two doses of telmisartan were assessed in 76 hypertensive, 
largely overweight patients aged 6 to < 18 years (body weight ≥ 20 kg and ≤ 120 kg, mean 74.6 kg), 
after taking telmisartan 1 mg/kg (n = 29 treated) or 2 mg/kg (n = 31 treated) over a four-week 
treatment period. By inclusion the presence of secondary hypertension was not investigated. In some 
of the investigated patients the doses used were higher than those recommended in the treatment of 
hypertension in the adult population, reaching a daily dose comparable to160 mg, which was tested in 
adults. After adjustment for age group effects mean SBP changes from baseline (primary objective) 



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were -14.5 (1.7) mmHg in the telmisartan 2 mg/kg group, -9.7 (1.7) mmHg in the telmisartan 1 mg/kg 
group, and -6.0 (2.4) in the placebo group. The adjusted DBP changes from baseline were -8.4 (1.5) 
mmHg, -4.5 (1.6) mmHg and -3.5 (2.1) mmHg respectively. The change was dose dependent. The 
safety data from this study in patients aged 6 to < 18 years appeared generally similar to that observed 
in adults. The safety of long term treatment of telmisartan in children and adolescents was not 
evaluated.

An increase in eosinophils reported in this patient population has not been recorded in adults. Its 
clinical significance and relevance is unknown.

These clinical data do not allow to make conclusions on the efficacy and safety of telmisartan in 
hypertensive paediatric population.

5.2 Pharmacokinetic properties

Absorption
Absorption of telmisartan is rapid although the amount absorbed varies. The mean absolute 
bioavailability for telmisartan is about 50 %. When telmisartan is taken with food, the reduction in the 
area under the plasma concentration-time curve (AUC0-∞) of telmisartan varies from approximately 
6 % (40 mg dose) to approximately 19 % (160 mg dose). By 3 hours after administration, plasma 
concentrations are similar whether telmisartan is taken fasting or with food.

Linearity/non-linearity
The small reduction in AUC is not expected to cause a reduction in the therapeutic efficacy. There is 
no linear relationship between doses and plasma levels. Cmax and to a lesser extent AUC increase 
disproportionately at doses above 40 mg.

Distribution
Telmisartan is largely bound to plasma protein (>99.5 %), mainly albumin and alpha-1 acid 
glycoprotein. The mean steady state apparent volume of distribution (Vdss) is approximately 500 l.

Biotransformation
Telmisartan is metabolised by conjugation to the glucuronide of the parent compound. No 
pharmacological activity has been shown for the conjugate.

Elimination
Telmisartan is characterised by biexponential decay pharmacokinetics with a terminal elimination 
half-life of >20 hours. The maximum plasma concentration (Cmax) and, to a smaller extent, the area 
under the plasma concentration-time curve (AUC), increase disproportionately with dose. There is no 
evidence of clinically relevant accumulation of telmisartan taken at the recommended dose. Plasma 
concentrations were higher in females than in males, without relevant influence on efficacy.

After oral (and intravenous) administration telmisartan is nearly exclusively excreted with the faeces, 
mainly as unchanged compound. Cumulative urinary excretion is <1 % of dose. Total plasma 
clearance (Cltot) is high (approximately 1,000 ml/min) compared with hepatic blood flow (about 
1,500 ml/min).

Special Populations

Paediatric population
The pharmacokinetics of two doses of telmisartan were assessed as a secondary objective in 
hypertensive patients (n = 57) aged 6 to < 18 years after taking telmisartan 1 mg/kg or 2 mg/kg over a 
four-week treatment period. Pharmacokinetic objectives included the determination of the steady-state 
of telmisartan in children and adolescents, and investigation of age-related differences. Although the 
study was too small for a meaningful assessment of the pharmacokinetics of children under 12 years of 
age, the results are generally consistent with the findings in adults and confirm the non-linearity of 
telmisartan, particularly for Cmax.



14

Gender
Differences in plasma concentrations were observed, with Cmax and AUC being approximately 3- and 
2-fold higher, respectively, in females compared to males.

Elderly
The pharmacokinetics of telmisartan do not differ between the elderly and those younger than 
65 years.

Renal impairment
In patients with mild to moderate and severe renal impairment, doubling of plasma concentrations was 
observed. However, lower plasma concentrations were observed in patients with renal insufficiency 
undergoing dialysis. Telmisartan is highly bound to plasma protein in renal-insufficient patients and 
cannot be removed by dialysis. The elimination half-life is not changed in patients with renal 
impairment.

Hepatic impairment
Pharmacokinetic studies in patients with hepatic impairment showed an increase in absolute 
bioavailability up to nearly 100 %. The elimination half-life is not changed in patients with hepatic 
impairment.

5.3 Preclinical safety data

In preclinical safety studies, doses producing exposure comparable to that in the clinical therapeutic 
range caused reduced red cell parameters (erythrocytes, haemoglobin, haematocrit), changes in renal 
haemodynamics (increased blood urea nitrogen and creatinine), as well as increased serum potassium 
in normotensive animals. In dogs, renal tubular dilation and atrophy were observed. Gastric mucosal 
injury (erosion, ulcers or inflammation) also was noted in rats and dogs. These pharmacologically-
mediated undesirable effects, known from preclinical studies with both angiotensin converting enzyme 
inhibitors and angiotensin II receptor antagonists, were prevented by oral saline supplementation.

In both species, increased plasma renin activity and hypertrophy/hyperplasia of the renal 
juxtaglomerular cells were observed. These changes, also a class effect of angiotensin converting 
enzyme inhibitors and other angiotensin II receptor antagonists, do not appear to have clinical 
significance.

No clear evidence of a teratogenic effect was observed, however at toxic dose levels of telmisartan an 
effect on the postnatal development of the offsprings such as lower body weight and delayed eye 
opening was observed.

There was no evidence of mutagenicity and relevant clastogenic activity in in vitro studies and no 
evidence of carcinogenicity in rats and mice.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Povidone (K30)
Meglumine
Sodium hydroxide
Lactose monohydrate
Sorbitol (E420)
Magnesium stearate

6.2 Incompatibilities



15

Not applicable.

6.3 Shelf life

2 years.

6.4 Special precautions for storage

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

6.5 Nature and contents of container

OPA/Al/PVC Al blister. Each blister contains 7 or 10 tablets.

Pack sizes: 14, 28, 30, 56, 84, 90, 98 and 100 tablets in a box.
Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

7. MARKETING AUTHORISATION HOLDER

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

8. MARKETING AUTHORISATION NUMBER(S)

14 tablets: EU/1/10/632/001
28 tablets: EU/1/10/632/002
30 tablets: EU/1/10/632/003
56 tablets: EU/1/10/632/004
84 tablets: EU/1/10/632/005
90 tablets: EU/1/10/632/006
98 tablets: EU/1/10/632/007
100 tablets: EU/1/10/632/022

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 4 June 2010
Date of latest renewal: 19 March 2015

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu



16

1. NAME OF THE MEDICINAL PRODUCT

Tolura 40 mg tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 40 mg telmisartan.

Excipients with known effect:
Each tablet contains 149.8 mg sorbitol (E420) and 57 mg lactose.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Tablet.

40 mg: white to almost white, biconvex, oval tablets

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Hypertension
Treatment of essential hypertension in adults.

Cardiovascular prevention
Reduction of cardiovascular morbidity in adults with:
- manifest atherothrombotic cardiovascular disease (history of coronary heart disease, stroke, or 

peripheral arterial disease) or
- type 2 diabetes mellitus with documented target organ damage.

4.2 Posology and method of administration

Posology

Treatment of essential hypertension

The usually effective dose is 40 mg once daily. Some patients may already benefit at a daily dose of 
20 mg. In cases where the target blood pressure is not achieved, the dose of telmisartan can be 
increased to a maximum of 80 mg once daily. Alternatively, telmisartan may be used in combination 
with thiazide-type diuretics such as hydrochlorothiazide, which has been shown to have an additive 
blood pressure lowering effect with telmisartan. When considering raising the dose, it must be borne 
in mind that the maximum antihypertensive effect is generally attained four to eight weeks after the 
start of treatment (see section 5.1).

Cardiovascular prevention

The recommended dose is 80 mg once daily. It is not known whether doses lower than 80 mg of 
telmisartan are effective in reducing cardiovascular morbidity.
When initiating telmisartan therapy for the reduction of cardiovascular morbidity, close monitoring of 
blood pressure is recommended, and if appropriate adjustment of medications that lower blood 
pressure may be necessary.



17

Special populations

Patients with renal impairment

Limited experience is available in patients with severe renal impairment or haemodialysis. A lower 
starting dose of 20 mg is recommended in these patients (see section 4.4). No posology adjustment is 
required for patients with mild to moderate renal impairment.

Patients with hepatic impairment

Tolura is contraindicated in patients with severe hepatic impairment (see section 4.3).
In patients with mild to moderate hepatic impairment the posology should not exceed 40 mg once 
daily (see section 4.4).

Elderly patients
No dose adjustment is necessary for elderly patients.

Paediatric population

The safety and efficacy of Tolura in children and adolescents aged below 18 years have not been 
established.
Currently available data are described in section 5.1 and 5.2 but no recommendation on a posology can 
be made.

Method of administration

Telmisartan tablets are for once-daily oral administration and should be taken with liquid, with or 
without food.

Precautions to be taken before handling or administering the medicinal product

Telmisartan should be kept in the sealed blister due to the hygroscopic property of the tablets. Tablets 
should be taken out of the blister shortly before administration (see section 6.6).

4.3 Contraindications

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1
- Second and third trimester of pregnancy (see sections 4.4 and 4.6)
- Biliary obstructive disorders
- Severe hepatic impairment

The concomitant use of Tolura with aliskiren-containing products is contraindicated in patients with 
diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m2) (see sections 4.5 and 5.1).

4.4 Special warnings and precautions for use

Pregnancy

Angiotensin II receptor antagonists should not be initiated during pregnancy. Unless continued 
angiotensin II receptor antagonist 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 angiotensin II receptor antagonists should 
be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 
4.6).

Hepatic impairment



18

Tolura is not to be given to patients with cholestasis, biliary obstructive disorders or severe hepatic 
impairment (see section 4.3) since telmisartan is mostly eliminated with the bile. These patients can be 
expected to have reduced hepatic clearance for telmisartan. Tolura should be used only with caution in 
patients with mild to moderate hepatic impairment.

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.

Renal impairment and kidney transplantation

When Tolura is used in patients with impaired renal function, periodic monitoring of potassium and 
creatinine serum levels is recommended. There is no experience regarding the administration of Tolura
in patients with recent kidney transplantation.

Intravascular hypovolaemia

Symptomatic hypotension, especially after the first dose of Tolura, 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 Tolura. Volume and/or 
sodium depletion should be corrected prior to administration of Tolura.

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

There is evidence that the concomitant use of ACE-inhibitors, angiotensin II receptor blockers or 
aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including 
acute renal failure). Dual blockade of RAAS through the combined use of ACE-inhibitors, angiotensin 
II receptor blockers or aliskiren is therefore not recommended (see sections 4.5 and 5.1).
If dual blockade therapy is considered absolutely necessary, this should only occur under specialist 
supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure.
ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with 
diabetic nephropathy.

Other conditions with stimulation of the renin-angiotensin-aldosterone system

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 medicinal products that affect this system such 
as telmisartan has been associated with acute hypotension, hyperazotaemia, oliguria, or rarely acute 
renal failure (see section 4.8).

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 telmisartan is not 
recommended.

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.

Diabetic patients treated with insulin or antidiabetics

In these patients hypoglycaemia may occur under telmisartan treatment. Therefore, in these patients an 



19

approptiate blood glucose monitoring should be considered; a dose adjustment of insulin or 
antidiabetics may be required, when indicated.

Hyperkalaemia

The use of medicinal products that affect the renin-angiotensin-aldosterone system may cause 
hyperkalaemia.

In the elderly, in patients with renal insufficiency, in diabetic patients, in patients concomitantly 
treated with other medicinal products that may increase potassium levels, and/or in patients with 
intercurrent events, hyperkalaemia may be fatal.

Before considering the concomitant use of medicinal products that affect the renin-angiotensin-
aldosterone system, the benefit risk ratio should be evaluated.

The main risk factors for hyperkalaemia to be considered are:
- Diabetes mellitus, renal impairment, age (>70 years).
- Combination with one or more other medicinal products that affect the renin-angiotensin-

aldosterone system and/or potassium supplements. Medicinal products or therapeutic classes of 
medicinal products that may provoke hyperkalaemia are salt substitutes containing potassium, 
potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, non steroidal 
anti-inflammatory medicinal products (NSAIDs, including selective COX-2 inhibitors), heparin, 
immunosuppressives (cyclosporin or tacrolimus), and trimethoprim.

- Intercurrent events, in particular dehydratation, acute cardiac decompensation, metabolic 
acidosis, worsening of renal function, sudden worsening of the renal condition (e.g. infectious 
diseases), cellular lysis (e.g. acute limb ischemia, rhabdomyolysis, extend trauma).

Close monitoring of serum potassium in at risk patients is recommended (see section 4.5).

Sorbitol

Tolura tablets contain sorbitol (E420). Patients with rare hereditary problems of fructose intolerance 
should not take Tolura.

Lactose

Tolura tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the 
Lapp lactase deficiency or glucose-galactose malabsorption should not take Tolura.

Ethnic differences

As observed for angiotensin converting enzyme inhibitors, telmisartan and the other angiotensin II 
receptor 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.

Other

As with any antihypertensive agent, excessive reduction of blood pressure in patients with ischaemic 
cardiopathy or ischaemic cardiovascular disease could result in a myocardial infarction or stroke.

4.5 Interaction with other medicinal products and other forms of interaction

Digoxin

When telmisartan was co-administered with digoxin, median increases in digoxin peak plasma 
concentration (49%) and in trough concentration (20%) were observed. When initiating, adjusting, and 



20

discontinuing telmisartan, monitor digoxin levels in order to maintain levels within the therapeutic 
range.

As with other medicinal products acting on the renin-angiotensin-aldosterone system, telmisartan may 
provoke hyperkalaemia (see section 4.4). The risk may increase in case of treatment combination with 
other medicinal products that may also provoke hyperkalaemia (salt substitutes containing potassium, 
potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, non steroidal anti-
inflammatory medicinal products (NSAIDs, including selective COX-2 inhibitors), heparin, 
immunosuppressives (cyclosporin or tacrolimus), and trimethoprim).

The occurrence of hyperkalaemia depends on associated risk factors. The risk is increased in case of 
the above-mentioned treatment combinations. The risk is particularly high in combination with 
potassium sparing-diuretics, and when combined with salt substitutes containing potassium. A 
combination with ACE inhibitors or NSAIDs, for example, presents a lesser risk provided that 
precautions for use are strictly followed.

Concomitant use not recommended

Potassium sparing diuretics or potassium supplements

Angiotensin II receptor antagonists such as telmisartan, attenuate diuretic induced potassium loss. 
Potassium sparing diuretics e.g. spirinolactone, eplerenone, triamterene, or amiloride, potassium 
supplements, or potassium-containing salt substitutes may lead to a significant increase in serum 
potassium. If concomitant use is indicated because of documented hypokalaemia they should be used 
with caution and with frequent monitoring of serum potassium.

Lithium

Reversible increases in serum lithium concentrations and toxicity have been reported during 
concomitant administration of lithium with angiotensin converting enzyme inhibitors, and with 
angiotensin II receptor antagonists, including telmisartan. If use of the combination proves necessary, 
careful monitoring of serum lithium levels is recommended.

Concomitant use requiring caution

Non-steroidal anti-inflammatory medicinal products

NSAIDs (i.e. acetylsalicylic acid at anti-inflammatory dosage regimens, COX-2 inhibitors and non-
selective NSAIDs) may reduce the antihypertensive effect of angiotensin II receptor antagonists.
In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with 
compromised renal function), the co-administration of angiotensin II receptor antagonists and agents 
that inhibit cyclo-oxygenase may result in further deterioration of renal function, including possible 
acute renal failure, which is usually reversible. Therefore, the combination should be administered 
with caution, especially in the elderly. Patients should be adequately hydrated and consideration 
should be given to monitoring of renal function after initiation of concomitant therapy and periodically 
thereafter.

In one study the co-administration of telmisartan and ramipril led to an increase of up to 2.5 fold in the 
AUC0-24 and Cmax of ramipril and ramiprilat. The clinical relevance of this observation is not known.

Diuretics (thiazide or loop diuretics)

Prior treatment with high dose diuretics such as furosemide (loop diuretic) and hydrochlorothiazide 
(thiazide diuretic) may result in volume depletion and in a risk of hypotension when initiating therapy 
with telmisartan.

To be taken into account with concomitant use



21

Other antihypertensive agents

The blood pressure lowering effect of telmisartan can be increased by concomitant use of other 
antihypertensive medicinal products.

Clinical trial data has shown that dual blockade of the renin-angiotensin-aldosterone-system (RAAS) 
through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is associated 
with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal 
function (including acute renal failure) compared to the use of a single RAAS-acting agent (see 
sections 4.3, 4.4 and 5.1).

Based on their pharmacological properties it can be expected that the following medicinal products 
may potentiate the hypotensive effects of all antihypertensives including telmisartan: Baclofen, 
amifostine. Furthermore, orthostatic hypotension may be aggravated by alcohol, barbiturates, narcotics 
or antidepressants.

Corticosteroids (systemic route)

Reduction of the antihypertensive effect.

4.6 Fertility, pregnancy and lactation

Pregnancy

The use of angiotensin II receptor antagonists is not recommended during the first trimester of 
pregnancy (see section 4.4). The use of angiotensin II receptor antagonists is contraindicated during 
the second and third trimesters of pregnancy (see sections 4.3 and 4.4).

There are no adequate data from the use of Tolura in pregnant women. Studies in animals have shown 
reproductive toxicity (see section 5.3).

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, similar risks may exist for this class of drugs. Unless continued angiotensin II 
receptor antagonist 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 angiotensin II receptor antagonists should be stopped 
immediately, and, if appropriate, alternative therapy should be started.

Exposure to angiotensin II receptor antagonist 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 angiotensin II receptor antagonists have occurred from the second trimester of 
pregnancy, ultrasound check of renal function and skull is recommended.
Infants whose mothers have taken angiotensin II receptor antagonists should be closely observed for 
hypotension (see sections 4.3 and 4.4).

Breast-feeding

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

Fertility



22

In preclinical studies, no effects of Tolura on male and female fertility were observed.

4.7 Effects on ability to drive and use machines

When driving vehicles or operating machinery it should be taken into account that dizziness or 
drowsiness may occasionally occur when taking antihypertensive therapy such as Tolura.

4.8 Undesirable effects

Summary of the safety profile

Serious adverse drug reactions include anaphylactic reaction and angioedema which may occur rarely 
(≥1/10,000 to <1/1,000), and acute renal failure.

The overall incidence of adverse reactions reported with telmisartan was usually comparable to 
placebo (41.4 % vs 43.9 %) in controlled trials in patients treated for hypertension. The incidence of 
adverse reactions was not dose related and showed no correlation with gender, age or race of the 
patients. The safety profile of telmisartan in patients treated for the reduction of cardiovascular 
morbidity was consistent with that obtained in hypertensive patients.

The adverse reactions listed below have been accumulated from controlled clinical trials in patients 
treated for hypertension and from post-marketing reports. The listing also takes into account serious 
adverse reactions and adverse reactions leading to discontinuation reported in three clinical long-term 
studies including 21642 patients treated with telmisartan for the reduction of cardiovascular morbidity 
for up to six years.

Tabulated summary of adverse reactions

Adverse reactions have been ranked under headings of frequency using the following convention:
very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100);
rare (≥1/10,000 to <1/1,000); very rare (<1/10,000).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Infections and infestations 

 Uncommon:

Rare:

Urinary tract infection including cystitis, upper respiratory tract infection 
including pharyngitis and sinusitis
Sepsis including fatal outcome1

Blood and the lymphatic system disorders 
Uncommon:
Rare: 

Anaemia
Eosinophilia, thrombocytopenia

Immune system disorders 
Rare: Anaphylactic reaction, hypersensitivity

Metabolism and nutrition disorders 
Uncommon:
Rare: 

Hyperkalaemia
Hypoglycaemia (in diabetic patients)

Psychiatric disorders 
Uncommon: 
Rare: 

Insomnia, depression
Anxiety 

Nervous system disorders 
Uncommon:
Rare:

Syncope
Somnolence



23

Eye disorders 
Rare: Visual disturbance

Ear and labyrinth disorders 
Uncommon: Vertigo 

Cardiac disorders 
Uncommon:
Rare: 

Bradycardia
Tachycardia

Vascular disorders 
Uncommon: Hypotension2, orthostatic hypotension

Respiratory, thoracic and mediastinal disorders 
Uncommon:
Very rare:

Dyspnoea, cough
Interstitial lung disease4

Gastrointestinal disorders 
Uncommon:
Rare: 

Abdominal pain, diarrhoea, dyspepsia, flatulence, vomiting
Dry mouth, stomach discomfort, dysgeusia

Hepato-biliary disorders 
Rare: Hepatic function abnormal/liver disorder3

Skin and subcutaneous tissue disorders 
Uncommon:
Rare:

Pruritus, hyperhidrosis, rash
Angioedema (also with fatal outcome), eczema, erythema, urticaria, drug 
eruption, toxic skin eruption

Muscoloskeletal and connective tissue disorders 
Uncommon:
Rare:

Back pain (e.g. sciatica), muscle spasms, myalgia,
Arthralgia, pain in extremity, tendon pain (tendinitis like symptoms)

Renal and urinary disorders 
Uncommon: Renal impairment including acute renal failure 

General disorders and administration site conditions 
Uncommon: 
Rare:

Chest pain, asthenia (weakness)
Influenza-like illness

Investigations 

Uncommon:
Rare:

Blood creatinine increased
Haemoglobin decreased, blood uric acid increased, hepatic enzyme increased, 
blood creatine phosphokinase increased

1, 2, 3, 4: for further descriptions, please see sub-section “Description of selected adverse reactions”

Description of selected adverse reactions

Sepsis
In the PRoFESS trial, an increased incidence of sepsis was observed with telmisartan compared with 
placebo. The event may be a chance finding or related to a mechanism currently not known (see also 
section 5.1).



24

Hypotension
This adverse reaction was reported as common in patients with controlled blood pressure who were 
treated with telmisartan for the reduction of cardiovascular morbidity on top of standard care.

Hepatic function abnormal/liver disorder
Most cases of hepatic function abnormal/liver disorder from post-marketing experience occurred in 
Japanese patients. Japanese patients are more likely to experience these adverse reactions.

Interstitial lung disease
Cases of interstitial lung disease have been reported from post-marketing experience in temporal 
association with the intake of telmisartan. However, a causal relationship has not been established.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.

4.9 Overdose

There is limited information available with regard to overdose in humans.

Symptoms: The most prominent manifestations of telmisartan overdose were hypotension and 
tachycardia; bradycardia, dizziness, increase in serum creatinine, and acute renal failure have also 
been reported.

Treatment: Telmisartan is not removed by haemodialysis. The patient should be closely monitored, 
and the treatment should be symptomatic and supportive. Management depends on the time since 
ingestion and the severity of the symptoms. Suggested measures include induction of emesis and / or 
gastric lavage. Activated charcoal may be useful in the treatment of overdosage. Serum electrolytes 
and creatinine should be monitored frequently. If hypotension occurs, the patient should be placed in a 
supine position, with salt and volume replacement given quickly.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Angiotensin II Antagonists, plain, ATC code: C09CA07.

Mechanism of action

Telmisartan is an orally active and specific angiotensin II receptor (type AT1) antagonist. Telmisartan 
displaces angiotensin II with very high affinity from its binding site at the AT1 receptor subtype, which 
is responsible for the known actions of angiotensin II. Telmisartan does not exhibit any partial agonist 
activity at the AT1 receptor. Telmisartan selectively binds the AT1 receptor. The binding is long-
lasting. Telmisartan does not show affinity for other receptors, including AT2 and other less 
characterised AT receptors. The functional role of these receptors is not known, nor is the effect of 
their possible overstimulation by angiotensin II, whose levels are increased by telmisartan. Plasma 
aldosterone levels are decreased by telmisartan. Telmisartan does not inhibit human plasma renin or 
block ion channels. Telmisartan does not inhibit angiotensin converting enzyme (kininase II), the 
enzyme which also degrades bradykinin. Therefore it is not expected to potentiate bradykinin-
mediated adverse effects.

In human, an 80 mg dose of telmisartan almost completely inhibits the angiotensin II evoked blood 
pressure increase. The inhibitory effect is maintained over 24 hours and still measurable up to 
48 hours.



25

Clinical efficacy and safety

Treatment of essential hypertension
After the first dose of telmisartan, the antihypertensive activity gradually becomes evident within 
3 hours. The maximum reduction in blood pressure is generally attained 4 to 8 weeks after the start of 
treatment and is sustained during long-term therapy.

The antihypertensive effect persists constantly over 24 hours after dosing and includes the last 4 hours 
before the next dose as shown by ambulatory blood pressure measurements. This is confirmed by 
trough to peak ratios consistently above 80 % seen after doses of 40 and 80 mg of telmisartan in 
placebo controlled clinical studies. There is an apparent trend to a dose relationship to a time to 
recovery of baseline systolic blood pressure (SBP). In this respect data concerning diastolic blood 
pressure (DBP) are inconsistent.

In patients with hypertension telmisartan reduces both systolic and diastolic blood pressure without 
affecting pulse rate. The contribution of the medicinal product's diuretic and natriuretic effect to its 
hypotensive activity has still to be defined. The antihypertensive efficacy of telmisartan is comparable 
to that of agents representative of other classes of antihypertensive medicinal products (demonstrated 
in clinical trials comparing telmisartan to amlodipine, atenolol, enalapril, hydrochlorothiazide, and 
lisinopril).

Upon abrupt cessation of treatment with telmisartan, blood pressure gradually returns to pre-treatment 
values over a period of several days without evidence of rebound hypertension.

The incidence of dry cough was significantly lower in patients treated with telmisartan than in those 
given angiotensin converting enzyme inhibitors in clinical trials directly comparing the two 
antihypertensive treatments.

Cardiovascular prevention
ONTARGET (ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint 
Trial) compared the effects of telmisartan, ramipril and the combination of telmisartan and ramipril on 
cardiovascular outcomes in 25620 patients aged 55 years or older with a history of coronary artery 
disease, stroke, TIA, peripheral arterial disease, or type 2 diabetes mellitus accompanied by evidence
of end-organ damage (e.g. retinopathy, left ventricular hypertrophy, macro- or microalbuminuria), 
which is a population at risk for cardiovascular events.

Patients were randomized to one of the three following treatment groups: telmisartan 80 mg (n = 
8542), ramipril 10 mg (n = 8576), or the combination of telmisartan 80 mg plus ramipril 10 mg (n = 
8502), and followed for a mean observation time of 4.5 years.

Telmisartan showed a similar effect to ramipril in reducing the primary composite endpoint of 
cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for 
congestive heart failure. The incidence of the primary endpoint was similar in the telmisartan (16.7 %) 
and ramipril (16.5 %) groups. The hazard ratio for telmisartan vs. ramipril was 1.01 (97.5 % CI 0.93 -
1.10, p (non-inferiority) = 0.0019 at a margin of 1.13). The all-cause mortality rate was 11.6 % and 
11.8 % among telmisartan and ramipril treated patients, respectively.

Telmisartan was found to be similarly effective to ramipril in the pre-specified secondary endpoint of 
cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke [0.99 (97.5 % CI 0.90 -
1.08), p (non-inferiority) = 0.0004], the primary endpoint in the reference study HOPE (The Heart 
Outcomes Prevention Evaluation Study), which had investigated the effect of ramipril vs. placebo.

TRANSCEND randomized ACE-I intolerant patients with otherwise similar inclusion criteria as 
ONTARGET to telmisartan 80 mg (n=2954) or placebo (n=2972), both given on top of standard care. 
The mean duration of follow up was 4 years and 8 months. No statistically significant difference in the 
incidence of the primary composite endpoint (cardiovascular death, non-fatal myocardial infarction, 



26

non-fatal stroke, or hospitalization for congestive heart failure) was found [15.7 % in the telmisartan 
and 17.0 % in the placebo groups with a hazard ratio of 0.92 (95 % CI 0.81 - 1.05, p = 0.22)]. There 
was evidence for a benefit of telmisartan compared to placebo in the pre-specified secondary 
composite endpoint of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke 
[0.87 (95 % CI 0.76 - 1.00, p = 0.048)]. There was no evidence for benefit on cardiovascular mortality 
(hazard ratio 1.03, 95 % CI 0.85 - 1.24).

Cough and angioedema were less frequently reported in patients treated with telmisartan than in 
patients treated with ramipril, whereas hypotension was more frequently reported with telmisartan.

Combining telmisartan with ramipril did not add further benefit over ramipril or telmisartan alone. CV 
mortality and all cause mortality were numerically higher with the combination. In addition, there was 
a significantly higher incidence of hyperkalaemia, renal failure, hypotension and syncope in the
combination arm. Therefore the use of a combination of telmisartan and ramipril is not recommended 
in this population.

In the “Prevention Regimen For Effectively avoiding Second Strokes” (PRoFESS) trial in patients 50 
years and older, who recently experienced stroke, an increased incidence of sepsis was noted for 
telmisartan compared with placebo, 0,70 % vs. 0,49 % RR 1,43 (95 % confidence interval 1,00 –
2,06) the incidence of fatal sepsis cases was increased for patients taking telmisartan (0,33 %) vs. 
patients taking placebo (0,16 %) RR 2,07 (95 % confidence interval 1,14 – 3,76). The observed 
increased occurrence rate of sepsis associated with the use of telmisartan may be either a chance 
finding or related to a mechanism not currently known.

Two large randomised, controlled trials (ONTARGET (ONgoing Telmisartan Alone and in 
combination with Ramipril Global Endpoint Trial) and VA NEPHRON-D (The Veterans Affairs 
Nephropathy in Diabetes)) have examined the use of the combination of an ACE-inhibitor with an 
angiotensin II receptor blocker.
ONTARGET was a study conducted in patients with a history of cardiovascular or cerebrovascular 
disease, or type 2 diabetes mellitus accompanied by evidence of end-organ damage. VA NEPHRON-D 
was a study in patients with type 2 diabetes mellitus and diabetic nephropathy.
These studies have shown no significant beneficial effect on renal and/or cardiovascular outcomes and 
mortality, while an increased risk of hyperkalaemia, acute kidney injury and/or hypotension as 
compared to monotherapy was observed. Given their similar pharmacodynamic properties, these 
results are also relevant for other ACE-inhibitors and angiotensin II receptor blockers.
ACE-inhibitors and angiotensin II receptor blockers should therefore not be used concomitantly in 
patients with diabetic nephropathy.
ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) 
was a study designed to test the benefit of adding aliskiren to a standard therapy of an ACE-inhibitor 
or an angiotensin II receptor blocker in patients with type 2 diabetes mellitus and chronic kidney 
disease, cardiovascular disease, or both. The study was terminated early because of an increased risk 
of adverse outcomes. Cardiovascular death and stroke were both numerically more frequent in the 
aliskiren group than in the placebo group and adverse events and serious adverse events of interest 
(hyperkalaemia, hypotension and renal dysfunction) were more frequently reported in the aliskiren 
group than in the placebo group.

Paediatric population

The safety and efficacy of telmisartan in children and adolescents aged below 18 years have not been 
established.

The blood pressure lowering effects of two doses of telmisartan were assessed in 76 hypertensive, 
largely overweight patients aged 6 to < 18 years (body weight ≥ 20 kg and ≤ 120 kg, mean 74.6 kg), 
after taking telmisartan 1 mg/kg (n = 29 treated) or 2 mg/kg (n = 31 treated) over a four-week 
treatment period. By inclusion the presence of secondary hypertension was not investigated. In some 
of the investigated patients the doses used were higher than those recommended in the treatment of 
hypertension in the adult population, reaching a daily dose comparable to160 mg, which was tested in 



27

adults. After adjustment for age group effects mean SBP changes from baseline (primary objective) 
were -14.5 (1.7) mmHg in the telmisartan 2 mg/kg group, -9.7 (1.7) mmHg in the telmisartan 1 mg/kg 
group, and -6.0 (2.4) in the placebo group. The adjusted DBP changes from baseline were -8.4 (1.5) 
mmHg, -4.5 (1.6) mmHg and -3.5 (2.1) mmHg respectively. The change was dose dependent. The 
safety data from this study in patients aged 6 to < 18 years appeared generally similar to that observed 
in adults. The safety of long term treatment of telmisartan in children and adolescents was not 
evaluated.

An increase in eosinophils reported in this patient population has not been recorded in adults. Its 
clinical significance and relevance is unknown.

These clinical data do not allow to make conclusions on the efficacy and safety of telmisartan in 
hypertensive paediatric population.

5.2 Pharmacokinetic properties

Absorption
Absorption of telmisartan is rapid although the amount absorbed varies. The mean absolute 
bioavailability for telmisartan is about 50 %. When telmisartan is taken with food, the reduction in the 
area under the plasma concentration-time curve (AUC0-∞) of telmisartan varies from approximately 
6 % (40 mg dose) to approximately 19 % (160 mg dose). By 3 hours after administration, plasma 
concentrations are similar whether telmisartan is taken fasting or with food.

Linearity/non-linearity
The small reduction in AUC is not expected to cause a reduction in the therapeutic efficacy. There is 
no linear relationship between doses and plasma levels. Cmax and to a lesser extent AUC increase 
disproportionately at doses above 40 mg.

Distribution
Telmisartan is largely bound to plasma protein (>99.5 %), mainly albumin and alpha-1 acid 
glycoprotein. The mean steady state apparent volume of distribution (Vdss) is approximately 500 l.

Biotransformation
Telmisartan is metabolised by conjugation to the glucuronide of the parent compound. No 
pharmacological activity has been shown for the conjugate.

Elimination
Telmisartan is characterised by biexponential decay pharmacokinetics with a terminal elimination 
half-life of >20 hours. The maximum plasma concentration (Cmax) and, to a smaller extent, the area 
under the plasma concentration-time curve (AUC), increase disproportionately with dose. There is no 
evidence of clinically relevant accumulation of telmisartan taken at the recommended dose. Plasma 
concentrations were higher in females than in males, without relevant influence on efficacy.

After oral (and intravenous) administration telmisartan is nearly exclusively excreted with the faeces, 
mainly as unchanged compound. Cumulative urinary excretion is <1 % of dose. Total plasma 
clearance (Cltot) is high (approximately 1,000 ml/min) compared with hepatic blood flow (about 
1,500 ml/min).

Special Populations

Paediatric population
The pharmacokinetics of two doses of telmisartan were assessed as a secondary objective in 
hypertensive patients (n = 57) aged 6 to < 18 years after taking telmisartan 1 mg/kg or 2 mg/kg over a 
four-week treatment period. Pharmacokinetic objectives included the determination of the steady-state 
of telmisartan in children and adolescents, and investigation of age-related differences. Although the 
study was too small for a meaningful assessment of the pharmacokinetics of children under 12 years of 
age, the results are generally consistent with the findings in adults and confirm the non-linearity of 



28

telmisartan, particularly for Cmax.

Gender
Differences in plasma concentrations were observed, with Cmax and AUC being approximately 3- and 
2-fold higher, respectively, in females compared to males.

Elderly
The pharmacokinetics of telmisartan do not differ between the elderly and those younger than 
65 years.

Renal impairment
In patients with mild to moderate and severe renal impairment, doubling of plasma concentrations was 
observed. However, lower plasma concentrations were observed in patients with renal insufficiency 
undergoing dialysis. Telmisartan is highly bound to plasma protein in renal-insufficient patients and 
cannot be removed by dialysis. The elimination half-life is not changed in patients with renal 
impairment.

Hepatic impairment
Pharmacokinetic studies in patients with hepatic impairment showed an increase in absolute 
bioavailability up to nearly 100 %. The elimination half-life is not changed in patients with hepatic 
impairment.

5.3 Preclinical safety data

In preclinical safety studies, doses producing exposure comparable to that in the clinical therapeutic 
range caused reduced red cell parameters (erythrocytes, haemoglobin, haematocrit), changes in renal 
haemodynamics (increased blood urea nitrogen and creatinine), as well as increased serum potassium 
in normotensive animals. In dogs, renal tubular dilation and atrophy were observed. Gastric mucosal 
injury (erosion, ulcers or inflammation) also was noted in rats and dogs. These pharmacologically-
mediated undesirable effects, known from preclinical studies with both angiotensin converting enzyme 
inhibitors and angiotensin II receptor antagonists, were prevented by oral saline supplementation.

In both species, increased plasma renin activity and hypertrophy/hyperplasia of the renal 
juxtaglomerular cells were observed. These changes, also a class effect of angiotensin converting 
enzyme inhibitors and other angiotensin II receptor antagonists, do not appear to have clinical 
significance.

No clear evidence of a teratogenic effect was observed, however at toxic dose levels of telmisartan an 
effect on the postnatal development of the offsprings such as lower body weight and delayed eye 
opening was observed.

There was no evidence of mutagenicity and relevant clastogenic activity in in vitro studies and no 
evidence of carcinogenicity in rats and mice.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Povidone (K30)
Meglumine
Sodium hydroxide
Lactose monohydrate
Sorbitol (E420)
Magnesium stearate

6.2 Incompatibilities



29

Not applicable.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

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

6.5 Nature and contents of container

OPA/Al/PVC Al blister. Each blister contains 7 or 10 tablets.

Pack sizes: 14, 28, 30, 56, 84, 90, 98 and 100 tablets in a box.
Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

7. MARKETING AUTHORISATION HOLDER

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

8. MARKETING AUTHORISATION NUMBER(S)

14 tablets: EU/1/10/632/008
28 tablets: EU/1/10/632/009
30 tablets: EU/1/10/632/010
56 tablets: EU/1/10/632/011
84 tablets: EU/1/10/632/012
90 tablets: EU/1/10/632/013
98 tablets: EU/1/10/632/014
100 tablets: EU/1/10/632/023

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 4 June 2010
Date of latest renewal: 19 March 2015

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu



30

1. NAME OF THE MEDICINAL PRODUCT

Tolura 80 mg tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 80 mg telmisartan.

Excipients with known effect:
Each tablet contains 299.7 mg sorbitol (E420) and 114 mg lactose.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Tablet.

80 mg: white to almost white, biconvex, capsule shape tablets

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Hypertension
Treatment of essential hypertension in adults.

Cardiovascular prevention
Reduction of cardiovascular morbidity in adults with:
- manifest atherothrombotic cardiovascular disease (history of coronary heart disease, stroke, or 

peripheral arterial disease) or
- type 2 diabetes mellitus with documented target organ damage.

4.2 Posology and method of administration

Posology

Treatment of essential hypertension

The usually effective dose is 40 mg once daily. Some patients may already benefit at a daily dose of 
20 mg. In cases where the target blood pressure is not achieved, the dose of telmisartan can be 
increased to a maximum of 80 mg once daily. Alternatively, telmisartan may be used in combination 
with thiazide-type diuretics such as hydrochlorothiazide, which has been shown to have an additive 
blood pressure lowering effect with telmisartan. When considering raising the dose, it must be borne 
in mind that the maximum antihypertensive effect is generally attained four to eight weeks after the 
start of treatment (see section 5.1).

Cardiovascular prevention

The recommended dose is 80 mg once daily. It is not known whether doses lower than 80 mg of 
telmisartan are effective in reducing cardiovascular morbidity.
When initiating telmisartan therapy for the reduction of cardiovascular morbidity, close monitoring of 
blood pressure is recommended, and if appropriate adjustment of medications that lower blood 
pressure may be necessary.



31

Special populations

Patients with renal impairment

Limited experience is available in patients with severe renal impairment or haemodialysis. A lower 
starting dose of 20 mg is recommended in these patients (see section 4.4). No posology adjustment is 
required for patients with mild to moderate renal impairment.

Patients with hepatic impairment

Tolura is contraindicated in patients with severe hepatic impairment (see section 4.3).
In patients with mild to moderate hepatic impairment the posology should not exceed 40 mg once 
daily (see section 4.4).

Elderly patients
No dose adjustment is necessary for elderly patients.

Paediatric population

The safety and efficacy of Tolura in children and adolescents aged below 18 years have not been 
established.
Currently available data are described in section 5.1 and 5.2 but no recommendation on a posology can 
be made.

Method of administration

Telmisartan tablets are for once-daily oral administration and should be taken with liquid, with or 
without food.

Precautions to be taken before handling or administering the medicinal product

Telmisartan should be kept in the sealed blister due to the hygroscopic property of the tablets. Tablets 
should be taken out of the blister shortly before administration (see section 6.6).

4.3 Contraindications

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1
- Second and third trimester of pregnancy (see sections 4.4 and 4.6)
- Biliary obstructive disorders
- Severe hepatic impairment

The concomitant use of Tolura with aliskiren-containing products is contraindicated in patients with 
diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m2) (see sections 4.5 and 5.1).

4.4 Special warnings and precautions for use

Pregnancy

Angiotensin II receptor antagonists should not be initiated during pregnancy. Unless continued 
angiotensin II receptor antagonist 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 angiotensin II receptor antagonists should 
be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 
4.6).

Hepatic impairment



32

Tolura is not to be given to patients with cholestasis, biliary obstructive disorders or severe hepatic 
impairment (see section 4.3) since telmisartan is mostly eliminated with the bile. These patients can be 
expected to have reduced hepatic clearance for telmisartan. Tolura should be used only with caution in 
patients with mild to moderate hepatic impairment.

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.

Renal impairment and kidney transplantation

When Tolura is used in patients with impaired renal function, periodic monitoring of potassium and 
creatinine serum levels is recommended. There is no experience regarding the administration of Tolura
in patients with recent kidney transplantation.

Intravascular hypovolaemia

Symptomatic hypotension, especially after the first dose of Tolura, 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 Tolura. Volume and/or 
sodium depletion should be corrected prior to administration of Tolura.

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

There is evidence that the concomitant use of ACE-inhibitors, angiotensin II receptor blockers or 
aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including 
acute renal failure). Dual blockade of RAAS through the combined use of ACE-inhibitors, angiotensin 
II receptor blockers or aliskiren is therefore not recommended (see sections 4.5 and 5.1).
If dual blockade therapy is considered absolutely necessary, this should only occur under specialist 
supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure.
ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with 
diabetic nephropathy.

Other conditions with stimulation of the renin-angiotensin-aldosterone system

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 medicinal products that affect this system such 
as telmisartan has been associated with acute hypotension, hyperazotaemia, oliguria, or rarely acute 
renal failure (see section 4.8).

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 telmisartan is not 
recommended.

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.

Diabetic patients treated with insulin or antidiabetics

In these patients hypoglycaemia may occur under telmisartan treatment. Therefore, in these patients an 



33

approptiate blood glucose monitoring should be considered; a dose adjustment of insulin or 
antidiabetics may be required, when indicated.

Hyperkalaemia

The use of medicinal products that affect the renin-angiotensin-aldosterone system may cause 
hyperkalaemia.

In the elderly, in patients with renal insufficiency, in diabetic patients, in patients concomitantly 
treated with other medicinal products that may increase potassium levels, and/or in patients with 
intercurrent events, hyperkalaemia may be fatal.

Before considering the concomitant use of medicinal products that affect the renin-angiotensin-
aldosterone system, the benefit risk ratio should be evaluated.

The main risk factors for hyperkalaemia to be considered are:
- Diabetes mellitus, renal impairment, age (>70 years).
- Combination with one or more other medicinal products that affect the renin-angiotensin-

aldosterone system and/or potassium supplements. Medicinal products or therapeutic classes of 
medicinal products that may provoke hyperkalaemia are salt substitutes containing potassium, 
potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, non steroidal 
anti-inflammatory medicinal products (NSAIDs, including selective COX-2 inhibitors), heparin, 
immunosuppressives (cyclosporin or tacrolimus), and trimethoprim.

- Intercurrent events, in particular dehydratation, acute cardiac decompensation, metabolic 
acidosis, worsening of renal function, sudden worsening of the renal condition (e.g. infectious 
diseases), cellular lysis (e.g. acute limb ischemia, rhabdomyolysis, extend trauma).

Close monitoring of serum potassium in at risk patients is recommended (see section 4.5).

Sorbitol

Tolura tablets contain sorbitol (E420). Patients with rare hereditary problems of fructose intolerance 
should not take Tolura.

Lactose

Tolura tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the 
Lapp lactase deficiency or glucose-galactose malabsorption should not take Tolura.

Ethnic differences

As observed for angiotensin converting enzyme inhibitors, telmisartan and the other angiotensin II 
receptor 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.

Other

As with any antihypertensive agent, excessive reduction of blood pressure in patients with ischaemic 
cardiopathy or ischaemic cardiovascular disease could result in a myocardial infarction or stroke.

4.5 Interaction with other medicinal products and other forms of interaction

Digoxin

When telmisartan was co-administered with digoxin, median increases in digoxin peak plasma 
concentration (49%) and in trough concentration (20%) were observed. When initiating, adjusting, and 



34

discontinuing telmisartan, monitor digoxin levels in order to maintain levels within the therapeutic 
range.

As with other medicinal products acting on the renin-angiotensin-aldosterone system, telmisartan may 
provoke hyperkalaemia (see section 4.4). The risk may increase in case of treatment combination with 
other medicinal products that may also provoke hyperkalaemia (salt substitutes containing potassium, 
potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, non steroidal anti-
inflammatory medicinal products (NSAIDs, including selective COX-2 inhibitors), heparin, 
immunosuppressives (cyclosporin or tacrolimus), and trimethoprim).

The occurrence of hyperkalaemia depends on associated risk factors. The risk is increased in case of 
the above-mentioned treatment combinations. The risk is particularly high in combination with 
potassium sparing-diuretics, and when combined with salt substitutes containing potassium. A 
combination with ACE inhibitors or NSAIDs, for example, presents a lesser risk provided that 
precautions for use are strictly followed.

Concomitant use not recommended

Potassium sparing diuretics or potassium supplements

Angiotensin II receptor antagonists such as telmisartan, attenuate diuretic induced potassium loss. 
Potassium sparing diuretics e.g. spirinolactone, eplerenone, triamterene, or amiloride, potassium 
supplements, or potassium-containing salt substitutes may lead to a significant increase in serum 
potassium. If concomitant use is indicated because of documented hypokalaemia they should be used 
with caution and with frequent monitoring of serum potassium.

Lithium

Reversible increases in serum lithium concentrations and toxicity have been reported during 
concomitant administration of lithium with angiotensin converting enzyme inhibitors, and with 
angiotensin II receptor antagonists, including telmisartan. If use of the combination proves necessary, 
careful monitoring of serum lithium levels is recommended.

Concomitant use requiring caution

Non-steroidal anti-inflammatory medicinal products

NSAIDs (i.e. acetylsalicylic acid at anti-inflammatory dosage regimens, COX-2 inhibitors and non-
selective NSAIDs) may reduce the antihypertensive effect of angiotensin II receptor antagonists.
In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with 
compromised renal function), the co-administration of angiotensin II receptor antagonists and agents 
that inhibit cyclo-oxygenase may result in further deterioration of renal function, including possible 
acute renal failure, which is usually reversible. Therefore, the combination should be administered 
with caution, especially in the elderly. Patients should be adequately hydrated and consideration 
should be given to monitoring of renal function after initiation of concomitant therapy and periodically 
thereafter.

In one study the co-administration of telmisartan and ramipril led to an increase of up to 2.5 fold in the 
AUC0-24 and Cmax of ramipril and ramiprilat. The clinical relevance of this observation is not known.

Diuretics (thiazide or loop diuretics)

Prior treatment with high dose diuretics such as furosemide (loop diuretic) and hydrochlorothiazide 
(thiazide diuretic) may result in volume depletion and in a risk of hypotension when initiating therapy 
with telmisartan.

To be taken into account with concomitant use



35

Other antihypertensive agents

The blood pressure lowering effect of telmisartan can be increased by concomitant use of other 
antihypertensive medicinal products.

Clinical trial data has shown that dual blockade of the renin-angiotensin-aldosterone-system (RAAS) 
through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is associated 
with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal 
function (including acute renal failure) compared to the use of a single RAAS-acting agent (see 
sections 4.3, 4.4 and 5.1).

Based on their pharmacological properties it can be expected that the following medicinal products 
may potentiate the hypotensive effects of all antihypertensives including telmisartan: Baclofen, 
amifostine. Furthermore, orthostatic hypotension may be aggravated by alcohol, barbiturates, narcotics 
or antidepressants.

Corticosteroids (systemic route)

Reduction of the antihypertensive effect.

4.6 Fertility, pregnancy and lactation

Pregnancy

The use of angiotensin II receptor antagonists is not recommended during the first trimester of 
pregnancy (see section 4.4). The use of angiotensin II receptor antagonists is contraindicated during 
the second and third trimesters of pregnancy (see sections 4.3 and 4.4).

There are no adequate data from the use of Tolura in pregnant women. Studies in animals have shown 
reproductive toxicity (see section 5.3).

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, similar risks may exist for this class of drugs. Unless continued angiotensin II 
receptor antagonist 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 angiotensin II receptor antagonists should be stopped 
immediately, and, if appropriate, alternative therapy should be started.

Exposure to angiotensin II receptor antagonist 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 angiotensin II receptor antagonists have occurred from the second trimester of 
pregnancy, ultrasound check of renal function and skull is recommended.
Infants whose mothers have taken angiotensin II receptor antagonists should be closely observed for 
hypotension (see sections 4.3 and 4.4).

Breast-feeding

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

Fertility



36

In preclinical studies, no effects of Tolura on male and female fertility were observed.

4.7 Effects on ability to drive and use machines

When driving vehicles or operating machinery it should be taken into account that dizziness or 
drowsiness may occasionally occur when taking antihypertensive therapy such as Tolura.

4.8 Undesirable effects

Summary of the safety profile

Serious adverse drug reactions include anaphylactic reaction and angioedema which may occur rarely 
(≥1/10,000 to <1/1,000), and acute renal failure.

The overall incidence of adverse reactions reported with telmisartan was usually comparable to 
placebo (41.4 % vs 43.9 %) in controlled trials in patients treated for hypertension. The incidence of 
adverse reactions was not dose related and showed no correlation with gender, age or race of the 
patients. The safety profile of telmisartan in patients treated for the reduction of cardiovascular 
morbidity was consistent with that obtained in hypertensive patients.

The adverse reactions listed below have been accumulated from controlled clinical trials in patients 
treated for hypertension and from post-marketing reports. The listing also takes into account serious 
adverse reactions and adverse reactions leading to discontinuation reported in three clinical long-term 
studies including 21642 patients treated with telmisartan for the reduction of cardiovascular morbidity 
for up to six years.

Tabulated summary of adverse reactions

Adverse reactions have been ranked under headings of frequency using the following convention:
very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100);
rare (≥1/10,000 to <1/1,000); very rare (<1/10,000).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Infections and infestations

Uncommon:

Rare: 

Urinary tract infection including cystitis, upper respiratory tract infection 
including pharyngitis and sinusitis
Sepsis including fatal outcome1

Blood and the lymphatic system disorders 
Uncommon:
Rare: 

Anaemia
Eosinophilia, thrombocytopenia

Immune system disorders 
Rare: Anaphylactic reaction, hypersensitivity 

Metabolism and nutrition disorders 
Uncommon:
Rare

Hyperkalaemia
Hypoglycaemia (in diabetic patients)

Psychiatric disorders 
Uncommon: 
Rare: 

Insomnia, depression
Anxiety 

Nervous system disorders 
Uncommon:
Rare:

Syncope
Somnolence



37

Eye disorders 
Rare: Visual disturbance

Ear and labyrinth disorders 
Uncommon: Vertigo 

Cardiac disorders 
Uncommon:
Rare: 

Bradycardia
Tachycardia

Vascular disorders 
Uncommon: Hypotension2, orthostatic hypotension

Respiratory, thoracic and mediastinal disorders 
Uncommon:
Very rare:

Dyspnoea, cough
Interstitial lung disease4

Gastrointestinal disorders 
Uncommon:
Rare: 

Abdominal pain, diarrhoea, dyspepsia, flatulence, vomiting
Dry mouth, stomach discomfort, dysgeusia

Hepato-biliary disorders 
Rare: Hepatic function abnormal/liver disorder3

Skin and subcutaneous tissue disorders 
Uncommon:
Rare:

Pruritus, hyperhidrosis, rash
Angioedema (also with fatal outcome), eczema, erythema, urticaria, drug 
eruption, toxic skin eruption

Muscoloskeletal and connective tissue disorders 
Uncommon:
Rare:

Back pain (e.g. sciatica), muscle spasms, myalgia
Arthralgia, pain in extremity, tendon pain (tendinitis like symptoms)

Renal and urinary disorders 
Uncommon: Renal impairment including acute renal failure 

General disorders and administration site conditions 
Uncommon: 
Rare:

Chest pain, asthenia (weakness)
Influenza-like illness

Investigations 

Uncommon:
Rare:

Blood creatinine increased
Haemoglobin decreased, blood uric acid increased, hepatic enzyme increased, 
blood creatine phosphokinase increased

1, 2, 3, 4: for further descriptions, please see sub-section “Description of selected adverse reactions”

Description of selected adverse reactions

Sepsis
In the PRoFESS trial, an increased incidence of sepsis was observed with telmisartan compared with 
placebo. The event may be a chance finding or related to a mechanism currently not known (see also 
section 5.1).

Hypotension



38

This adverse reaction was reported as common in patients with controlled blood pressure who were 
treated with telmisartan for the reduction of cardiovascular morbidity on top of standard care.

Hepatic function abnormal/liver disorder
Most cases of hepatic function abnormal/liver disorder from post-marketing experience occurred in 
patients in Japan, who are more likely to experience these adverse reactions.

Interstitial lung disease
Cases of interstitial lung disease have been reported from post-marketing experience in temporal 
association with the intake of telmisartan. However, a causal relationship has not been established.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.

4.9 Overdose

There is limited information available with regard to overdose in humans.

Symptoms: The most prominent manifestations of telmisartan overdose were hypotension and 
tachycardia; bradycardia, dizziness, increase in serum creatinine, and acute renal failure have also 
been reported.

Treatment: Telmisartan is not removed by haemodialysis. The patient should be closely monitored, 
and the treatment should be symptomatic and supportive. Management depends on the time since 
ingestion and the severity of the symptoms. Suggested measures include induction of emesis and / or 
gastric lavage. Activated charcoal may be useful in the treatment of overdosage. Serum electrolytes 
and creatinine should be monitored frequently. If hypotension occurs, the patient should be placed in a 
supine position, with salt and volume replacement given quickly.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Angiotensin II Antagonists, plain, ATC code: C09CA07.

Mechanism of action

Telmisartan is an orally active and specific angiotensin II receptor (type AT1) antagonist. Telmisartan 
displaces angiotensin II with very high affinity from its binding site at the AT1 receptor subtype, which 
is responsible for the known actions of angiotensin II. Telmisartan does not exhibit any partial agonist 
activity at the AT1 receptor. Telmisartan selectively binds the AT1 receptor. The binding is long-
lasting. Telmisartan does not show affinity for other receptors, including AT2 and other less 
characterised AT receptors. The functional role of these receptors is not known, nor is the effect of 
their possible overstimulation by angiotensin II, whose levels are increased by telmisartan. Plasma 
aldosterone levels are decreased by telmisartan. Telmisartan does not inhibit human plasma renin or 
block ion channels. Telmisartan does not inhibit angiotensin converting enzyme (kininase II), the 
enzyme which also degrades bradykinin. Therefore it is not expected to potentiate bradykinin-
mediated adverse effects.

In human, an 80 mg dose of telmisartan almost completely inhibits the angiotensin II evoked blood 
pressure increase. The inhibitory effect is maintained over 24 hours and still measurable up to 
48 hours.



39

Clinical efficacy and safety

Treatment of essential hypertension
After the first dose of telmisartan, the antihypertensive activity gradually becomes evident within 
3 hours. The maximum reduction in blood pressure is generally attained 4 to 8 weeks after the start of 
treatment and is sustained during long-term therapy.

The antihypertensive effect persists constantly over 24 hours after dosing and includes the last 4 hours 
before the next dose as shown by ambulatory blood pressure measurements. This is confirmed by 
trough to peak ratios consistently above 80 % seen after doses of 40 and 80 mg of telmisartan in 
placebo controlled clinical studies. There is an apparent trend to a dose relationship to a time to 
recovery of baseline systolic blood pressure (SBP). In this respect data concerning diastolic blood 
pressure (DBP) are inconsistent.

In patients with hypertension telmisartan reduces both systolic and diastolic blood pressure without 
affecting pulse rate. The contribution of the medicinal product's diuretic and natriuretic effect to its 
hypotensive activity has still to be defined. The antihypertensive efficacy of telmisartan is comparable 
to that of agents representative of other classes of antihypertensive medicinal products (demonstrated 
in clinical trials comparing telmisartan to amlodipine, atenolol, enalapril, hydrochlorothiazide, and 
lisinopril).

Upon abrupt cessation of treatment with telmisartan, blood pressure gradually returns to pre-treatment 
values over a period of several days without evidence of rebound hypertension.

The incidence of dry cough was significantly lower in patients treated with telmisartan than in those 
given angiotensin converting enzyme inhibitors in clinical trials directly comparing the two 
antihypertensive treatments.

Cardiovascular prevention
ONTARGET (ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint 
Trial) compared the effects of telmisartan, ramipril and the combination of telmisartan and ramipril on 
cardiovascular outcomes in 25620 patients aged 55 years or older with a history of coronary artery 
disease, stroke, TIA, peripheral arterial disease, or type 2 diabetes mellitus accompanied by evidence 
of end-organ damage (e.g. retinopathy, left ventricular hypertrophy, macro- or microalbuminuria), 
which is a population at risk for cardiovascular events.

Patients were randomized to one of the three following treatment groups: telmisartan 80 mg (n = 
8542), ramipril 10 mg (n = 8576), or the combination of telmisartan 80 mg plus ramipril 10 mg (n = 
8502), and followed for a mean observation time of 4.5 years.

Telmisartan showed a similar effect to ramipril in reducing the primary composite endpoint of 
cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for 
congestive heart failure. The incidence of the primary endpoint was similar in the telmisartan (16.7 
%)and ramipril (16.5 %) groups. The hazard ratio for telmisartan vs. ramipril was 1.01 (97.5 % CI 
0.93 - 1.10, p (non-inferiority) = 0.0019 at a margin of 1.13). The all-cause mortality rate was 11.6 % 
and 11.8 % among telmisartan and ramipril treated patients, respectively.

Telmisartan was found to be similarly effective to ramipril in the pre-specified secondary endpoint of 
cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke [0.99 (97.5 % CI 0.90 -
1.08), p (non-inferiority) = 0.0004], the primary endpoint in the reference study HOPE (The Heart 
Outcomes Prevention Evaluation Study), which had investigated the effect of ramipril vs. placebo.

TRANSCEND randomized ACE-I intolerant patients with otherwise similar inclusion criteria as 
ONTARGET to telmisartan 80 mg (n=2954) or placebo (n=2972), both given on top of standard care.
The mean duration of follow up was 4 years and 8 months. No statistically significant difference in the 
incidence of the primary composite endpoint (cardiovascular death, non-fatal myocardial infarction, 
non-fatal stroke, or hospitalization for congestive heart failure) was found [15.7 % in the telmisartan 



40

and 17.0 % in the placebo groups with a hazard ratio of 0.92 (95 % CI 0.81 - 1.05, p = 0.22)]. There 
was evidence for a benefit of telmisartan compared to placebo in the pre-specified secondary 
composite endpoint of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke 
[0.87 (95 % CI 0.76 - 1.00, p = 0.048)]. There was no evidence for benefit on cardiovascular mortality 
(hazard ratio 1.03, 95 % CI 0.85 - 1.24).

Cough and angioedema were less frequently reported in patients treated with telmisartan than in 
patients treated with ramipril, whereas hypotension was more frequently reported with telmisartan.

Combining telmisartan with ramipril did not add further benefit over ramipril or telmisartan alone. CV 
mortality and all cause mortality were numerically higher with the combination. In addition, there was 
a significantly higher incidence of hyperkalaemia, renal failure, hypotension and syncope in the 
combination arm. Therefore the use of a combination of telmisartan and ramipril is not recommended 
in this population.

In the “Prevention Regimen For Effectively avoiding Second Strokes” (PRoFESS) trial in patients 50 
years and older, who recently experienced stroke, an increased incidence of sepsis was noted for 
telmisartan compared with placebo, 0,70 % vs. 0,49 % RR 1,43 (95 % confidence interval 1,00 –
2,06) the incidence of fatal sepsis cases was increased for patients taking telmisartan (0,33 %) vs. 
patients taking placebo (0,16 %) RR 2,07 (95 % confidence interval 1,14 – 3,76). The observed 
increased occurrence rate of sepsis associated with the use of telmisartan may be either a chance 
finding or related to a mechanism not currently known.

Two large randomised, controlled trials (ONTARGET (ONgoing Telmisartan Alone and in 
combination with Ramipril Global Endpoint Trial) and VA NEPHRON-D (The Veterans Affairs 
Nephropathy in Diabetes)) have examined the use of the combination of an ACE-inhibitor with an 
angiotensin II receptor blocker.
ONTARGET was a study conducted in patients with a history of cardiovascular or cerebrovascular 
disease, or type 2 diabetes mellitus accompanied by evidence of end-organ damage. VA NEPHRON-D 
was a study in patients with type 2 diabetes mellitus and diabetic nephropathy.
These studies have shown no significant beneficial effect on renal and/or cardiovascular outcomes and 
mortality, while an increased risk of hyperkalaemia, acute kidney injury and/or hypotension as 
compared to monotherapy was observed. Given their similar pharmacodynamic properties, these 
results are also relevant for other ACE-inhibitors and angiotensin II receptor blockers.
ACE-inhibitors and angiotensin II receptor blockers should therefore not be used concomitantly in 
patients with diabetic nephropathy.
ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) 
was a study designed to test the benefit of adding aliskiren to a standard therapy of an ACE-inhibitor 
or an angiotensin II receptor blocker in patients with type 2 diabetes mellitus and chronic kidney 
disease, cardiovascular disease, or both. The study was terminated early because of an increased risk 
of adverse outcomes. Cardiovascular death and stroke were both numerically more frequent in the 
aliskiren group than in the placebo group and adverse events and serious adverse events of interest 
(hyperkalaemia, hypotension and renal dysfunction) were more frequently reported in the aliskiren 
group than in the placebo group.

Paediatric population
The safety and efficacy of telmisartan in children and adolescents aged below 18 years have not been 
established.

The blood pressure lowering effects of two doses of telmisartan were assessed in 76 hypertensive, 
largely overweight patients aged 6 to < 18 years (body weight ≥ 20 kg and ≤ 120 kg, mean 74.6 kg), 
after taking telmisartan 1 mg/kg (n = 29 treated) or 2 mg/kg (n = 31 treated) over a four-week 
treatment period. By inclusion the presence of secondary hypertension was not investigated. In some 
of the investigated patients the doses used were higher than those recommended in the treatment of 
hypertension in the adult population, reaching a daily dose comparable to160 mg, which was tested in 
adults. After adjustment for age group effects mean SBP changes from baseline (primary objective) 
were -14.5 (1.7) mmHg in the telmisartan 2 mg/kg group, -9.7 (1.7) mmHg in the telmisartan 1 mg/kg 



41

group, and -6.0 (2.4) in the placebo group. The adjusted DBP changes from baseline were -8.4 (1.5) 
mmHg, -4.5 (1.6) mmHg and -3.5 (2.1) mmHg respectively. The change was dose dependent. The 
safety data from this study in patients aged 6 to < 18 years appeared generally similar to that observed 
in adults. The safety of long term treatment of telmisartan in children and adolescents was not 
evaluated.

An increase in eosinophils reported in this patient population has not been recorded in adults. Its 
clinical significance and relevance is unknown.

These clinical data do not allow to make conclusions on the efficacy and safety of telmisartan in 
hypertensive paediatric population.

5.2 Pharmacokinetic properties

Absorption
Absorption of telmisartan is rapid although the amount absorbed varies. The mean absolute 
bioavailability for telmisartan is about 50 %. When telmisartan is taken with food, the reduction in the 
area under the plasma concentration-time curve (AUC0-∞) of telmisartan varies from approximately 
6 % (40 mg dose) to approximately 19 % (160 mg dose). By 3 hours after administration, plasma 
concentrations are similar whether telmisartan is taken fasting or with food.

Linearity/non-linearity
The small reduction in AUC is not expected to cause a reduction in the therapeutic efficacy. There is 
no linear relationship between doses and plasma levels. Cmax and to a lesser extent AUC increase 
disproportionately at doses above 40 mg.

Distribution
Telmisartan is largely bound to plasma protein (>99.5 %), mainly albumin and alpha-1 acid 
glycoprotein. The mean steady state apparent volume of distribution (Vdss) is approximately 500 l.

Biotransformation
Telmisartan is metabolised by conjugation to the glucuronide of the parent compound. No 
pharmacological activity has been shown for the conjugate.

Elimination
Telmisartan is characterised by biexponential decay pharmacokinetics with a terminal elimination 
half-life of >20 hours. The maximum plasma concentration (Cmax) and, to a smaller extent, the area 
under the plasma concentration-time curve (AUC), increase disproportionately with dose. There is no 
evidence of clinically relevant accumulation of telmisartan taken at the recommended dose. Plasma 
concentrations were higher in females than in males, without relevant influence on efficacy.

After oral (and intravenous) administration telmisartan is nearly exclusively excreted with the faeces, 
mainly as unchanged compound. Cumulative urinary excretion is <1 % of dose. Total plasma 
clearance (Cltot) is high (approximately 1,000 ml/min) compared with hepatic blood flow (about 
1,500 ml/min).

Special Populations

Paediatric population
The pharmacokinetics of two doses of telmisartan were assessed as a secondary objective in 
hypertensive patients (n = 57) aged 6 to < 18 years after taking telmisartan 1 mg/kg or 2 mg/kg over a 
four-week treatment period. Pharmacokinetic objectives included the determination of the steady-state 
of telmisartan in children and adolescents, and investigation of age-related differences. Although the 
study was too small for a meaningful assessment of the pharmacokinetics of children under 12 years of 
age, the results are generally consistent with the findings in adults and confirm the non-linearity of 
telmisartan, particularly for Cmax.



42

Gender
Differences in plasma concentrations were observed, with Cmax and AUC being approximately 3- and 
2-fold higher, respectively, in females compared to males.

Elderly
The pharmacokinetics of telmisartan do not differ between the elderly and those younger than 
65 years.

Renal impairment
In patients with mild to moderate and severe renal impairment, doubling of plasma concentrations was 
observed. However, lower plasma concentrations were observed in patients with renal insufficiency 
undergoing dialysis. Telmisartan is highly bound to plasma protein in renal-insufficient patients and 
cannot be removed by dialysis. The elimination half-life is not changed in patients with renal 
impairment.

Hepatic impairment
Pharmacokinetic studies in patients with hepatic impairment showed an increase in absolute 
bioavailability up to nearly 100 %. The elimination half-life is not changed in patients with hepatic 
impairment.

5.3 Preclinical safety data

In preclinical safety studies, doses producing exposure comparable to that in the clinical therapeutic 
range caused reduced red cell parameters (erythrocytes, haemoglobin, haematocrit), changes in renal 
haemodynamics (increased blood urea nitrogen and creatinine), as well as increased serum potassium 
in normotensive animals. In dogs, renal tubular dilation and atrophy were observed. Gastric mucosal 
injury (erosion, ulcers or inflammation) also was noted in rats and dogs. These pharmacologically-
mediated undesirable effects, known from preclinical studies with both angiotensin converting enzyme 
inhibitors and angiotensin II receptor antagonists, were prevented by oral saline supplementation.

In both species, increased plasma renin activity and hypertrophy/hyperplasia of the renal 
juxtaglomerular cells were observed. These changes, also a class effect of angiotensin converting 
enzyme inhibitors and other angiotensin II receptor antagonists, do not appear to have clinical 
significance.

No clear evidence of a teratogenic effect was observed, however at toxic dose levels of telmisartan an 
effect on the postnatal development of the offsprings such as lower body weight and delayed eye 
opening was observed.

There was no evidence of mutagenicity and relevant clastogenic activity in in vitro studies and no 
evidence of carcinogenicity in rats and mice.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Povidone (K30)
Meglumine
Sodium hydroxide
Lactose monohydrate
Sorbitol (E420)
Magnesium stearate

6.2 Incompatibilities

Not applicable.



43

6.3 Shelf life

3 years.

6.4 Special precautions for storage

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

6.5 Nature and contents of container

OPA/Al/PVC Al blister. Each blister contains 7 or 10 tablets.

Pack sizes: 14, 28, 30, 56, 84, 90, 98 and 100 tablets in a box.
Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

7. MARKETING AUTHORISATION HOLDER

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

8. MARKETING AUTHORISATION NUMBER(S)

14 tablets: EU/1/10/632/015
28 tablets: EU/1/10/632/016
30 tablets: EU/1/10/632/017
56 tablets: EU/1/10/632/018
84 tablets: EU/1/10/632/019
90 tablets: EU/1/10/632/020
98 tablets: EU/1/10/632/021
100 tablets: EU/1/10/632/024

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 4 June 2010
Date of latest renewal: 19 March 2015

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu



44

ANNEX II

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH 
RELEASE

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
AND USE

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORIZATION

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



45

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturers responsible for batch release

KRKA, d.d., Novo mesto
Šmarješka cesta 6
8501 Novo mesto
Slovenia

KRKA-POLSKA Sp. z o.o.
ul. Równoległa 5
02-235 Warszawa
Poland

The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch.

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

Medicinal product subject to medical prescription.

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORIZATION

 Periodic Safety Update Reports

The marketing authorisation holder shall submit periodic safety update reports for this product 
in accordance with the requirements set out in the list of Union reference dates (EURD list)) 
provided for under Article 107c(7) of Directive 2001/83/EC and published on the European 
medicines web-portal.

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

 Risk Management Plan (RMP)

Not applicable.



46

ANNEX III

LABELLING AND PACKAGE LEAFLET



47

A. LABELLING



48

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON/BOX

1. NAME OF THE MEDICINAL PRODUCT

Tolura 20 mg tablets

telmisartan

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 20 mg telmisartan.

3. LIST OF EXCIPIENTS

Contains lactose monohydrate and sorbitol (E420). Read the package leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

14 tablets
28 tablets
30 tablets
56 tablets
84 tablets
90 tablets
98 tablets
100 tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Oral use
Read the package leaflet before use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

I



49

9. SPECIAL STORAGE CONDITIONS

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

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

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

12. MARKETING AUTHORISATION NUMBER(S)

14 tablets: EU/1/10/632/001
28 tablets: EU/1/10/632/002
30 tablets: EU/1/10/632/003
56 tablets: EU/1/10/632/004
84 tablets: EU/1/10/632/005
90 tablets: EU/1/10/632/006
98 tablets: EU/1/10/632/007
100 tablets: EU/1/10/632/022

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Tolura 20 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

<2D barcode carrying the unique identifier included.>

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

<PC:
SN:
NN:>



50

MINIMUM PARTICULARS TO APPEAR ON BLISTERS

BLISTER/OPA/Al/PVC Al

1. NAME OF THE MEDICINAL PRODUCT

Tolura 20 mg tablets

telmisartan

2. NAME OF THE MARKETING AUTHORISATION HOLDER

KRKA

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER

Only on blisters containing 7 tablets
MON
TUE
WED
THU
FRI
SAT
SUN



51

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON/BOX

1. NAME OF THE MEDICINAL PRODUCT

Tolura 40 mg tablets

telmisartan

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 40 mg telmisartan.

3. LIST OF EXCIPIENTS

Contains lactose monohydrate and sorbitol (E420). Read the package leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

14 tablets
28 tablets
30 tablets
56 tablets
84 tablets
90 tablets
98 tablets
100 tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Oral use
Read the package leaflet before use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

I



52

9. SPECIAL STORAGE CONDITIONS

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

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

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

12. MARKETING AUTHORISATION NUMBER(S)

14 tablets: EU/1/10/632/008
28 tablets: EU/1/10/632/009
30 tablets: EU/1/10/632/010
56 tablets: EU/1/10/632/011
84 tablets: EU/1/10/632/012
90 tablets: EU/1/10/632/013
98 tablets: EU/1/10/632/014
100 tablets: EU/1/10/632/023

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Tolura 40 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

<2D barcode carrying the unique identifier included.>

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

<PC:
SN:
NN:>



53

MINIMUM PARTICULARS TO APPEAR ON BLISTERS

BLISTER/OPA/Al/PVC Al

1. NAME OF THE MEDICINAL PRODUCT

Tolura 40 mg tablets

telmisartan

2. NAME OF THE MARKETING AUTHORISATION HOLDER

KRKA

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER

Only on blisters containing 7 tablets
MON
TUE
WED
THU
FRI
SAT
SUN



54

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON/BOX

1. NAME OF THE MEDICINAL PRODUCT

Tolura 80 mg tablets

telmisartan

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 80 mg telmisartan.

3. LIST OF EXCIPIENTS

Contains lactose monohydrate and sorbitol (E420). Read the package leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

14 tablets
28 tablets
30 tablets
56 tablets
84 tablets
90 tablets
98 tablets
100 tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Oral use
Read the package leaflet before use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

I



55

9. SPECIAL STORAGE CONDITIONS

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

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

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

12. MARKETING AUTHORISATION NUMBER(S)

14 tablets: EU/1/10/632/015
28 tablets: EU/1/10/632/016
30 tablets: EU/1/10/632/017
56 tablets: EU/1/10/632/018
84 tablets: EU/1/10/632/019
90 tablets: EU/1/10/632/020
98 tablets: EU/1/10/632/021
100 tablets: EU/1/10/632/024

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Tolura 80 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

<2D barcode carrying the unique identifier included.>

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

<PC:
SN:
NN:>



56

MINIMUM PARTICULARS TO APPEAR ON BLISTERS

BLISTER/OPA/Al/PVC Al

1. NAME OF THE MEDICINAL PRODUCT

Tolura 80 mg tablets

telmisartan

2. NAME OF THE MARKETING AUTHORISATION HOLDER

KRKA

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER

Only on blisters containing 7 tablets
MON
TUE
WED
THU
FRI
SAT
SUN



57

B. PACKAGE LEAFLET



58

Package leaflet: Information for the user

Tolura 20 mg tablets
Telmisartan

Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor or pharmacist.
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.
- If you get any side effects talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4.

What is in this leaflet:
1. What Tolura is and what it is used for
2. What you need to know before you take Tolura
3. How to take Tolura
4. Possible side effects
5. How to store Tolura
6. Contents of the pack and other information

1. What Tolura is and what it is used for

Tolura belongs to a class of medicines known as angiotensin II receptor antagonists. Angiotensin II is 
a substance produced in your body which causes your blood vessels to narrow, thus increasing your 
blood pressure. Tolura blocks the effect of angiotensin II so that the blood vessels relax, and your 
blood pressure is lowered.

Tolura is used to treat essential hypertension (high blood pressure) in adults. ‘Essential’ means that 
the high blood pressure is not caused by any other condition.

High blood pressure, if not treated, can damage blood vessels in several organs, which could lead 
sometimes to heart attack, heart or kidney failure, stroke, or blindness. There are usually no symptoms 
of high blood pressure before damage occurs. Thus it is important to regularly measure blood pressure 
to verify if it is within the normal range.

Tolura is also used to reduce cardiovascular events (i.e. heart attack or stroke) in adults who are at 
risk because they have a reduced or blocked blood supply to the heart or legs, or have had a stroke or 
have high risk diabetes. Your doctor can tell you if you are at high risk for such events.

2. What you need to know before you take Tolura

Do not take Tolura
- if you are allergic to telmisartan or any other ingredients of this medicine (listed in section 6).
- if you are more than 3 months pregnant. (It is also better to avoid Tolura in early pregnancy –

see pregnancy section.)
- if you have severe liver problems such as cholestasis or biliary obstruction (problems with the 

drainage of the bile from the liver and gall bladder) or any other severe liver disease.
- if you have diabetes or impaired kidney function and you are treated with a blood pressure 

lowering medicine containing aliskiren.

If any of the above applies to you, tell your doctor or pharmacist before taking Tolura.

Warnings and precautions



59

Talk to your doctor if you are suffering or have ever suffered from any of the following conditions or 
illnesses:

- Kidney disease or kidney transplant.
- Renal artery stenosis (narrowing of the blood vessels to one or both kidneys).
- Liver disease.
- Heart trouble.
- Raised aldosterone levels (water and salt retention in the body along with imbalance of various 

blood minerals).
- Low blood pressure (hypotension), likely to occur if you are dehydrated (excessive loss of body 

water) or have salt deficiency due to diuretic therapy ('water tablets'), low-salt diet, diarrhoea, or 
vomiting.

- Elevated potassium levels in your blood.
- Diabetes.

Talk to your doctor before taking Tolura:
- if you are taking digoxin.
- if you are taking any of the following medicines used to treat high blood pressure:

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

- aliskiren.

You must tell your doctor if you think you are (or might become) pregnant. Tolura 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).

In case of surgery or anaesthesia, you should tell your doctor that you are taking Tolura.

Tolura may be less effective in lowering the blood pressure in black patients.

Your doctor may check your kidney function, blood pressure, and the amount of electrolytes (e.g. 
potassium) in your blood at regular intervals.
See also information under the heading “Do not take Tolura”.

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

Other medicines and Tolura
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. Your doctor may need to change the dose of these other medicines or take other 
precautions. In some cases you may have to stop taking one of the medicines. This applies especially 
to the medicines listed below taken at the same time with Tolura:

- Lithium containing medicines to treat some types of depression.
- Medicines that may increase blood potassium levels such as salt substitutes containing 

potassium, potassium-sparing diuretics (certain 'water tablets'), ACE inhibitors, angiotensin II 
receptor antagonists, NSAIDs (non steroidal anti-inflammatory medicines, e.g. aspirin or 
ibuprofen), heparin, immunosuppressives (e.g. cyclosporin or tacrolimus), and the antibiotic 
trimethoprim.

- Diuretics ('water tablets'), especially if taken in high doses together with Tolura, may lead to 
excessive loss of body water and low blood pressure (hypotension).

- If you are taking an ACE-inhibitor or aliskiren (see also information under the headings “Do not 
take Tolura” and “Warnings and precautions”).

- Digoxin.

The effect of Tolura may be reduced when you take NSAIDs (non steroidal anti-inflammatory 
medicines, e.g. aspirin or ibuprofen) or corticosteroids.



60

Tolura may increase the blood pressure lowering effect of other medicines used to treat high blood 
pressure or of medicines with blood pressure lowering potential (e.g. baclofen, amifostine). 
Furthermore, low blood pressure may be aggravated by alcohol, barbiturates, narcotics or 
antidepressants. You may notice this as dizziness when standing up. You should consult with your 
doctor if you need to adjust the dose of your other medicine while taking Tolura.

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 Tolura before you become pregnant or as soon as you know you are pregnant 
and will advise you to take another medicine instead of Tolura. Tolura 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. Tolura 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
Some people feel dizzy or tired when taking Tolura. If you feel dizzy or tired, do not drive or operate 
machinery.

Tolura contains lactose and sorbitol (E420).
If you are intolerant to some sugars, consult your doctor before taking Tolura.

3. How to take Tolura

Always take Tolura exactly as your doctor has told you. Check with your doctor or pharmacist if you 
are not sure.

The recommended dose of Tolura is one tablet a day. Try to take the tablet at the same time each day.
You can take Tolura with or without food. The tablets should be swallowed with some water or other 
non-alcoholic drink. It is important that you take Tolura every day until your doctor tells you 
otherwise. If you have the impression that the effect of Tolura is too strong or too weak, talk to your 
doctor or pharmacist.

For treatment of high blood pressure, the usual dose of Tolura for most patients is one 40 mg tablet 
once a day to control blood pressure over the 24 hour period. Your doctor has recommended a lower 
dose of one 20 mg tablet daily. Tolura may also be used in combination with diuretics ('water tablets') 
such as hydrochlorothiazide which has been shown to have an additive blood pressure lowering effect 
with Tolura.

For reduction of cardiovascular events, the usual dose of Tolura is one 80 mg tablet once a day. At the 
beginning of the preventive therapy with Tolura 80 mg, blood pressure should be frequently 
monitored.

If your liver is not working properly, the usual dose should not exceed 40 mg once daily.

If you take more Tolura than you should
If you accidentally take too many tablets, contact your doctor, pharmacist, or your nearest hospital 
emergency department immediately.

If you forget to take Tolura



61

If you forget to take a dose, do not worry. Take it as soon as you remember then carry on as before. If 
you do not take your tablet on one day, take your normal dose on the next day. Do not take a double 
dose to make up for forgotten individual doses.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

Some side effects can be serious and need immediate medical attention:

You should see your doctor immediately if you experience any of the following symptoms:

Sepsis* (often called "blood poisoning", is a severe infection with whole-body inflammatory 
response), rapid swelling of the skin and mucosa (angioedema); these side effects are rare (may affect 
up to 1 in 1,000 people) but are extremely serious and patients should stop taking the medicine and see 
their doctor immediately. If these effects are not treated they could be fatal.

Possible side effects of Tolura:

Common side effects (may affect up to 1 in 10 people):
Low blood pressure (hypotension) in users treated for reduction of cardiovascular events.

Uncommon side effects (may affect up to 1 in 100 people):
Urinary tract infections, upper respiratory tract infections (e.g. sore throat, inflamed sinuses, common 
cold), deficiency in red blood cells (anaemia), high potassium levels, difficulty falling asleep, feeling 
sad (depression), fainting (syncope), feeling of spinning (vertigo), slow heart rate (bradycardia), low 
blood pressure (hypotension) in users treated for high blood pressure, dizziness on standing up 
(orthostatic hypotension), shortness of breath, cough, abdominal pain, diarrhoea, discomfort in the 
abdomen, bloating, vomiting, itching, increased sweating, drug rash, back pain, muscle cramps, 
muscle pain (myalgia), kidney impairment including acute kidney failure, pain in the chest, feeling of 
weakness, and increased level of creatinine in the blood.

Rare side effects (may affect up to 1 in 1,000 people):
Sepsis* (often called "blood poisoning", is a severe infection with whole-body inflammatory response 
which can lead to death), increase in certain white blood cells (eosinophilia), low platelet count 
(thrombocytopenia), severe allergic reaction (anaphylactic reaction), allergic reaction (e.g. rash, 
itching, difficulty breathing, wheezing, swelling of the face or low blood pressure), low blood sugar 
levels (in diabetic patients), feeling anxious, somnolence, impaired vision, fast heart beat 
(tachycardia), dry mouth, upset stomach, taste disturbance (dysgeusia), abnormal liver function 
(Japanese patients are more likely to experience these side effect), rapid swelling of the skin and 
mucosa which can also lead to death (angioedema also with fatal outcome), eczema (a skin disorder), 
redness of skin, hives (urticaria), severe drug rash, joint pain (arthralgia), pain in extremity, tendon 
pain, flu-like-illness, decreased haemoglobin (a blood protein), increased levels of uric acid, increased 
hepatic enzymes or creatine phosphokinase in the blood.

Very rare side effects (may affect up to 1 in 10,000 people):
Progressive scarring of lung tissue (interstitial lung disease)**.

*The event may have happened by chance or could be related to a mechanism currently not known.

**Cases of progressive scarring of lung tissue have been reported during intake of telmisartan. 
However, it is not known whether telmisartan was the cause.

Reporting of side effects



62

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine.

5. How to store Tolura

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

Do not use this medicine after the expiry date which is stated on the carton and blister after “EXP”. 
The expiry date refers to the last day of that month.

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

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Tolura contains
- The active substance is telmisartan. Each tablet contains 20 mg telmisartan.
- The other ingredients are povidone, meglumine, sodium hydroxide, lactose monohydrate, 

sorbitol (E420) and magnesium stearate.

What Tolura looks like and contents of the pack
Tolura 20 mg tablets are white to almost white, round tablets.

Tolura is available in blister packs containing 14, 28, 30, 56, 84, 90, 98 and 100 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

Manufacturers
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
KRKA-POLSKA Sp. z o.o., ul. Równoległa 5, 02-235 Warszawa, Poland

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

België/Belgique/Belgien
KRKA Belgium, SA.
Tél/Tel: + 32 (0) 487 50 73 62

Lietuva
UAB KRKA Lietuva
Tel: + 370 5 236 27 40

България
КРКА България ЕООД
Teл.: + 359 (02) 962 34 50

Luxembourg/Luxemburg
KRKA Belgium, SA.
Tél/Tel: + 32 (0) 487 50 73 62 (BE)

Česká republika
KRKA ČR, s.r.o.
Tel: + 420 (0) 221 115 150

Magyarország
KRKA Magyarország Kereskedelmi Kft.
Tel.: + 361 (0) 355 8490

Danmark
KRKA Sverige AB

Malta
E.J. Busuttil Ltd.



63

Tlf: + 46 (0)8 643 67 66 (SE) Tel: + 356 21 445 885

Deutschland
TAD Pharma GmbH
Tel: + 49 (0) 4721 606-0

Nederland
KRKA Belgium, SA.
Tel: + 32 (0) 487 50 73 62 (BE)

Eesti
KRKA, d.d., Novo mesto Eesti filiaal
Tel: + 372 (0) 6 671 658

Norge
KRKA Sverige AB
Tlf: + 46 (0)8 643 67 66 (SE)

Ελλάδα
QUALIA PHARMA S.A.
Τηλ: + 30 210 6256177

Österreich
KRKA Pharma GmbH, Wien
Tel: + 43 (0)1 66 24 300

España
KRKA Farmacéutica, S.L.
Tel: + 34 911 61 03 81

Polska
KRKA-POLSKA Sp. z o.o.
Tel.: + 48 (0)22 573 7500

France
KRKA France Eurl
Tél: + 33 (0)1 57 40 82 25

Portugal
KRKA Farmacêutica, Sociedade Unipessoal Lda.
Tel: + 351 (0)21 46 43 650

Hrvatska
KRKA - FARMA d.o.o.
Tel: + 385 1 6312 100

România
KRKA Romania S.R.L., Bucharest
Tel: + 4 021 310 66 05

Ireland
KRKA Pharma Dublin, Ltd.
Tel: + 353 1 293 91 80

Slovenija
KRKA, d.d., Novo mesto
Tel: + 386 (0) 1 47 51 100

Ísland
KRKA Sverige AB
Sími: + 46 (0)8 643 67 66 (SE)

Slovenská republika
KRKA Slovensko, s.r.o.
Tel: + 421 (0) 2 571 04 501

Italia
KRKA Farmaceutici Milano S.r.l.
Tel: + 39 02 3300 8841

Suomi/Finland
KRKA Finland Oy
Puh/Tel: + 358 20 754 5330

Κύπρος
Kipa Pharmacal Ltd.
Τηλ: + 357 24 651 882

Sverige
KRKA Sverige AB
Tel: + 46 (0)8 643 67 66 (SE)

Latvija
KRKA Latvija SIA
Tel: + 371 6 733 86 10

United Kingdom
Consilient Health (UK) Ltd.
Tel: + 44(0)203 751 1888

This leaflet was last revised in

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu



64

Package leaflet: Information for the user

Tolura 40 mg tablets
Telmisartan

Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor or pharmacist.
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.
- If you get any side effects talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4.

What is in this leaflet:
1. What Tolura is and what it is used for
2. What you need to know before you take Tolura
3. How to take Tolura
4. Possible side effects
5. How to store Tolura
6. Contents of the pack and other information

1. What Tolura is and what it is used for

Tolura belongs to a class of medicines known as angiotensin II receptor antagonists. Angiotensin II is 
a substance produced in your body which causes your blood vessels to narrow, thus increasing your 
blood pressure. Tolura blocks the effect of angiotensin II so that the blood vessels relax, and your 
blood pressure is lowered.

Tolura is used to treat essential hypertension (high blood pressure) in adults. ‘Essential’ means that 
the high blood pressure is not caused by any other condition.

High blood pressure, if not treated, can damage blood vessels in several organs, which could lead 
sometimes to heart attack, heart or kidney failure, stroke, or blindness. There are usually no symptoms 
of high blood pressure before damage occurs. Thus it is important to regularly measure blood pressure 
to verify if it is within the normal range.

Tolura is also used to reduce cardiovascular events (i.e. heart attack or stroke) in adults who are at 
risk because they have a reduced or blocked blood supply to the heart or legs, or have had a stroke or 
have high risk diabetes. Your doctor can tell you if you are at high risk for such events.

2. What you need to know before you take Tolura

Do not take Tolura
- if you are allergic to telmisartan or any other ingredients of this medicine (listed in section 6).
- if you are more than 3 months pregnant. (It is also better to avoid Tolura in early pregnancy –

see pregnancy section.)
- if you have severe liver problems such as cholestasis or biliary obstruction (problems with the 

drainage of the bile from the liver and gall bladder) or any other severe liver disease.
- if you have diabetes or impaired kidney function and you are treated with a blood pressure 

lowering medicine containing aliskiren.

If any of the above applies to you, tell your doctor or pharmacist before taking Tolura.

Warnings and precautions



65

Talk to your doctor if you are suffering or have ever suffered from any of the following conditions or 
illnesses:

- Kidney disease or kidney transplant.
- Renal artery stenosis (narrowing of the blood vessels to one or both kidneys).
- Liver disease.
- Heart trouble.
- Raised aldosterone levels (water and salt retention in the body along with imbalance of various 

blood minerals).
- Low blood pressure (hypotension), likely to occur if you are dehydrated (excessive loss of body 

water) or have salt deficiency due to diuretic therapy ('water tablets'), low-salt diet, diarrhoea, or 
vomiting.

- Elevated potassium levels in your blood.
- Diabetes.

Talk to your doctor before taking Tolura:
- if you are taking digoxin.
- if you are taking any of the following medicines used to treat high blood pressure:

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

- aliskiren.

You must tell your doctor if you think you are (or might become) pregnant. Tolura 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).

In case of surgery or anaesthesia, you should tell your doctor that you are taking Tolura.

Tolura may be less effective in lowering the blood pressure in black patients.

Your doctor may check your kidney function, blood pressure, and the amount of electrolytes (e.g. 
potassium) in your blood at regular intervals.
See also information under the heading “Do not take Tolura”.

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

Other medicines and Tolura
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. Your doctor may need to change the dose of these other medicines or take other 
precautions. In some cases you may have to stop taking one of the medicines. This applies especially 
to the medicines listed below taken at the same time with Tolura:

- Lithium containing medicines to treat some types of depression.
- Medicines that may increase blood potassium levels such as salt substitutes containing 

potassium, potassium-sparing diuretics (certain 'water tablets'), ACE inhibitors, angiotensin II 
receptor antagonists, NSAIDs (non steroidal anti-inflammatory medicines, e.g. aspirin or 
ibuprofen), heparin, immunosuppressives (e.g. cyclosporin or tacrolimus), and the antibiotic 
trimethoprim.

- Diuretics ('water tablets'), especially if taken in high doses together with Tolura, may lead to 
excessive loss of body water and low blood pressure (hypotension).

- If you are taking an ACE-inhibitor or aliskiren (see also information under the headings “Do not 
take Tolura” and “Warnings and precautions”).

- Digoxin.

The effect of Tolura may be reduced when you take NSAIDs (non steroidal anti-inflammatory 
medicines, e.g. aspirin or ibuprofen) or corticosteroids.



66

Tolura may increase the blood pressure lowering effect of other medicines used to treat high blood 
pressure or of medicines with blood pressure lowering potential (e.g. baclofen, amifostine). 
Furthermore, low blood pressure may be aggravated by alcohol, barbiturates, narcotics or 
antidepressants. You may notice this as dizziness when standing up. You should consult with your 
doctor if you need to adjust the dose of your other medicine while taking Tolura.

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 Tolura before you become pregnant or as soon as you know you are pregnant 
and will advise you to take another medicine instead of Tolura. Tolura 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. Tolura 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
Some people feel dizzy or tired when taking Tolura. If you feel dizzy or tired, do not drive or operate 
machinery.

Tolura contains lactose and sorbitol (E420).
If you are intolerant to some sugars, consult your doctor before taking Tolura.

3. How to take Tolura

Always take Tolura exactly as your doctor has told you. Check with your doctor or pharmacist if you 
are not sure.

The recommended dose of Tolura is one tablet a day. Try to take the tablet at the same time each day. 
You can take Tolura with or without food. The tablets should be swallowed with some water or other 
non-alcoholic drink. It is important that you take Tolura every day until your doctor tells you 
otherwise. If you have the impression that the effect of Tolura is too strong or too weak, talk to your 
doctor or pharmacist.

For treatment of high blood pressure, the usual dose of Tolura for most patients is one 40 mg tablet 
once a day to control blood pressure over the 24 hour period. However, sometimes your doctor may 
recommend a lower dose of 20 mg or a higher dose of 80 mg. Tolura may also be used in combination 
with diuretics ('water tablets') such as hydrochlorothiazide which has been shown to have an additive 
blood pressure lowering effect with Tolura.

For reduction of cardiovascular events, the usual dose of Tolura is one 80 mg tablet once a day. At the 
beginning of the preventive therapy with Tolura 80 mg, blood pressure should be frequently 
monitored.

If your liver is not working properly, the usual dose should not exceed 40 mg once daily.

If you take more Tolura than you should
If you accidentally take too many tablets, contact your doctor, pharmacist, or your nearest hospital 
emergency department immediately.

If you forget to take Tolura



67

If you forget to take a dose, do not worry. Take it as soon as you remember then carry on as before. If 
you do not take your tablet on one day, take your normal dose on the next day. Do not take a double 
dose to make up for forgotten individual doses.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

Some side effects can be serious and need immediate medical attention:

You should see your doctor immediately if you experience any of the following symptoms:

Sepsis* (often called "blood poisoning", is a severe infection with whole-body inflammatory 
response), rapid swelling of the skin and mucosa (angioedema); these side effects are rare (may affect 
up to 1 in 1,000 people) but are extremely serious and patients should stop taking the medicine and see 
their doctor immediately. If these effects are not treated they could be fatal.

Possible side effects of Tolura:

Common side effects (may affect up to 1 in 10 people):
Low blood pressure (hypotension) in users treated for reduction of cardiovascular events.

Uncommon side effects (may affect up to 1 in 100 people):
Urinary tract infections, upper respiratory tract infections (e.g. sore throat, inflamed sinuses, common 
cold), deficiency in red blood cells (anaemia), high potassium levels, difficulty falling asleep, feeling 
sad (depression), fainting (syncope), feeling of spinning (vertigo), slow heart rate (bradycardia), low 
blood pressure (hypotension) in users treated for high blood pressure, dizziness on standing up 
(orthostatic hypotension), shortness of breath, cough, abdominal pain, diarrhoea, discomfort in the 
abdomen, bloating, vomiting, itching, increased sweating, drug rash, back pain, muscle cramps, 
muscle pain (myalgia), kidney impairment including acute kidney failure, pain in the chest, feeling of 
weakness, and increased level of creatinine in the blood.

Rare side effects (may affect up to 1 in 1,000 people):
Sepsis* (often called "blood poisoning", is a severe infection with whole-body inflammatory response 
which can lead to death), increase in certain white blood cells (eosinophilia), low platelet count 
(thrombocytopenia), severe allergic reaction (anaphylactic reaction), allergic reaction (e.g. rash, 
itching, difficulty breathing, wheezing, swelling of the face or low blood pressure), low blood sugar 
levels (in diabetic patients), feeling anxious, somnolence, impaired vision, fast heart beat 
(tachycardia), dry mouth, upset stomach, taste disturbance (dysgeusia), abnormal liver function 
(Japanese patients are more likely to experience these side effect), rapid swelling of the skin and 
mucosa which can also lead to death (angioedema also with fatal outcome), eczema (a skin disorder), 
redness of skin, hives (urticaria), severe drug rash, joint pain (arthralgia), pain in extremity, tendon 
pain, flu-like-illness, decreased haemoglobin (a blood protein), increased levels of uric acid, increased
hepatic enzymes or creatine phosphokinase in the blood.

Very rare side effects (may affect up to 1 in 10,000 people):
Progressive scarring of lung tissue (interstitial lung disease)**.

* The event may have happened by chance or could be related to a mechanism currently not known.

** Cases of progressive scarring of lung tissue have been reported during intake of telmisartan. 
However, it is not known whether telmisartan was the cause.

Reporting of side effects



68

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine.

5. How to store Tolura

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

Do not use this medicine after the expiry date which is stated on the carton and blister after “EXP”. 
The expiry date refers to the last day of that month.

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

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Tolura contains
- The active substance is telmisartan. Each tablet contains 40 mg telmisartan.
- The other ingredients are povidone, meglumine, sodium hydroxide, lactose monohydrate, 

sorbitol (E420) and magnesium stearate.

What Tolura looks like and contents of the pack
Tolura 40 mg tablets are white to almost white, biconvex, oval tablets.

Tolura is available in blister packs containing 14, 28, 30, 56, 84, 90, 98 and 100 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

Manufacturers
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
KRKA-POLSKA Sp. z o.o., ul. Równoległa 5, 02-235 Warszawa, Poland

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

België/Belgique/Belgien
KRKA Belgium, SA.
Tél/Tel: + 32 (0) 487 50 73 62

Lietuva
UAB KRKA Lietuva
Tel: + 370 5 236 27 40

България
КРКА България ЕООД
Teл.: + 359 (02) 962 34 50

Luxembourg/Luxemburg
KRKA Belgium, SA.
Tél/Tel: + 32 (0) 487 50 73 62 (BE)

Česká republika
KRKA ČR, s.r.o.
Tel: + 420 (0) 221 115 150

Magyarország
KRKA Magyarország Kereskedelmi Kft.
Tel.: + 361 (0) 355 8490

Danmark
KRKA Sverige AB

Malta
E.J. Busuttil Ltd.



69

Tlf: + 46 (0)8 643 67 66 (SE) Tel: + 356 21 445 885

Deutschland
TAD Pharma GmbH
Tel: + 49 (0) 4721 606-0

Nederland
KRKA Belgium, SA.
Tel: + 32 (0) 487 50 73 62 (BE)

Eesti
KRKA, d.d., Novo mesto Eesti filiaal
Tel: + 372 (0) 6 671 658

Norge
KRKA Sverige AB
Tlf: + 46 (0)8 643 67 66 (SE)

Ελλάδα
QUALIA PHARMA S.A.
Τηλ: + 30 210 6256177

Österreich
KRKA Pharma GmbH, Wien
Tel: + 43 (0)1 66 24 300

España
KRKA Farmacéutica, S.L.
Tel: + 34 911 61 03 81

Polska
KRKA-POLSKA Sp. z o.o.
Tel.: + 48 (0)22 573 7500

France
KRKA France Eurl
Tél: + 33 (0)1 57 40 82 25

Portugal
KRKA Farmacêutica, Sociedade Unipessoal Lda.
Tel: + 351 (0)21 46 43 650

Hrvatska
KRKA - FARMA d.o.o.
Tel: + 385 1 6312 100

România
KRKA Romania S.R.L., Bucharest
Tel: + 4 021 310 66 05

Ireland
KRKA Pharma Dublin, Ltd.
Tel: + 353 1 293 91 80

Slovenija
KRKA, d.d., Novo mesto
Tel: + 386 (0) 1 47 51 100

Ísland
KRKA Sverige AB
Sími: + 46 (0)8 643 67 66 (SE)

Slovenská republika
KRKA Slovensko, s.r.o.
Tel: + 421 (0) 2 571 04 501

Italia
KRKA Farmaceutici Milano S.r.l.
Tel: + 39 02 3300 8841

Suomi/Finland
KRKA Finland Oy
Puh/Tel: + 358 20 754 5330

Κύπρος
Kipa Pharmacal Ltd.
Τηλ: + 357 24 651 882

Sverige
KRKA Sverige AB
Tel: + 46 (0)8 643 67 66 (SE)

Latvija
KRKA Latvija SIA
Tel: + 371 6 733 86 10

United Kingdom
Consilient Health (UK) Ltd.
Tel: + 44(0)203 751 1888

This leaflet was last revised in

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu



70

Package leaflet: Information for the user

Tolura 80 mg tablets
Telmisartan

Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor or pharmacist.
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.
- If you get any side effects talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4.

What is in this leaflet:
1. What Tolura is and what it is used for
2. What you need to know before you take Tolura
3. How to take Tolura
4. Possible side effects
5. How to store Tolura
6. Contents of the pack and other information

1. What Tolura is and what it is used for

Tolura belongs to a class of medicines known as angiotensin II receptor antagonists. Angiotensin II is 
a substance produced in your body which causes your blood vessels to narrow, thus increasing your 
blood pressure. Tolura blocks the effect of angiotensin II so that the blood vessels relax, and your 
blood pressure is lowered.

Tolura is used to treat essential hypertension (high blood pressure) in adults. ‘Essential’ means that 
the high blood pressure is not caused by any other condition.

High blood pressure, if not treated, can damage blood vessels in several organs, which could lead 
sometimes to heart attack, heart or kidney failure, stroke, or blindness. There are usually no symptoms 
of high blood pressure before damage occurs. Thus it is important to regularly measure blood pressure 
to verify if it is within the normal range.

Tolura is also used to reduce cardiovascular events (i.e. heart attack or stroke) in adults who are at 
risk because they have a reduced or blocked blood supply to the heart or legs, or have had a stroke or 
have high risk diabetes. Your doctor can tell you if you are at high risk for such events.

2. What you need to know before you take Tolura

Do not take Tolura
- if you are allergic to telmisartan or any other ingredients of this medicine (listed in section 6).
- if you are more than 3 months pregnant. (It is also better to avoid Tolura in early pregnancy –

see pregnancy section.)
- if you have severe liver problems such as cholestasis or biliary obstruction (problems with the 

drainage of the bile from the liver and gall bladder) or any other severe liver disease.
- if you have diabetes or impaired kidney function and you are treated with a blood pressure 

lowering medicine containing aliskiren.

If any of the above applies to you, tell your doctor or pharmacist before taking Tolura.

Warnings and precautions



71

Talk to your doctor if you are suffering or have ever suffered from any of the following conditions or 
illnesses:

- Kidney disease or kidney transplant.
- Renal artery stenosis (narrowing of the blood vessels to one or both kidneys).
- Liver disease.
- Heart trouble.
- Raised aldosterone levels (water and salt retention in the body along with imbalance of various 

blood minerals).
- Low blood pressure (hypotension), likely to occur if you are dehydrated (excessive loss of body 

water) or have salt deficiency due to diuretic therapy ('water tablets'), low-salt diet, diarrhoea, or 
vomiting.

- Elevated potassium levels in your blood.
- Diabetes.

Talk to your doctor before taking Tolura:
- if you are taking digoxin.
- if you are taking any of the following medicines used to treat high blood pressure:

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

- aliskiren.

You must tell your doctor if you think you are (or might become) pregnant. Tolura 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).

In case of surgery or anaesthesia, you should tell your doctor that you are taking Tolura.

Tolura may be less effective in lowering the blood pressure in black patients.

Your doctor may check your kidney function, blood pressure, and the amount of electrolytes (e.g. 
potassium) in your blood at regular intervals.
See also information under the heading “Do not take Tolura”.

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

Other medicines and Tolura
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. Your doctor may need to change the dose of these other medicines or take other 
precautions. In some cases you may have to stop taking one of the medicines. This applies especially 
to the medicines listed below taken at the same time with Tolura:

- Lithium containing medicines to treat some types of depression.
- Medicines that may increase blood potassium levels such as salt substitutes containing 

potassium, potassium-sparing diuretics (certain 'water tablets'), ACE inhibitors, angiotensin II 
receptor antagonists, NSAIDs (non steroidal anti-inflammatory medicines, e.g. aspirin or 
ibuprofen), heparin, immunosuppressives (e.g. cyclosporin or tacrolimus), and the antibiotic 
trimethoprim.

- Diuretics ('water tablets'), especially if taken in high doses together with Tolura, may lead to 
excessive loss of body water and low blood pressure (hypotension).

- If you are taking an ACE-inhibitor or aliskiren (see also information under the headings “Do not 
take Tolura” and “Warnings and precautions”).

- Digoxin.

The effect of Tolura may be reduced when you take NSAIDs (non steroidal anti-inflammatory 
medicines, e.g. aspirin or ibuprofen) or corticosteroids.



72

Tolura may increase the blood pressure lowering effect of other medicines used to treat high blood 
pressure or of medicines with blood pressure lowering potential (e.g. baclofen, amifostine). 
Furthermore, low blood pressure may be aggravated by alcohol, barbiturates, narcotics or 
antidepressants. You may notice this as dizziness when standing up. You should consult with your 
doctor if you need to adjust the dose of your other medicine while taking Tolura.

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 Tolura before you become pregnant or as soon as you know you are pregnant 
and will advise you to take another medicine instead of Tolura. Tolura 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. Tolura 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
Some people feel dizzy or tired when taking Tolura. If you feel dizzy or tired, do not drive or operate 
machinery.

Tolura contains lactose and sorbitol (E420).
If you are intolerant to some sugars, consult your doctor before taking Tolura.

3. How to take Tolura

Always take Tolura exactly as your doctor has told you. Check with your doctor or pharmacist if you 
are not sure.

The recommended dose of Tolura is one tablet a day. Try to take the tablet at the same time each day. 
You can take Tolura with or without food. The tablets should be swallowed with some water or other 
non-alcoholic drink. It is important that you take Tolura every day until your doctor tells you 
otherwise. If you have the impression that the effect of Tolura is too strong or too weak, talk to your 
doctor or pharmacist.

For treatment of high blood pressure, the usual dose of Tolura for most patients is one 40 mg tablet 
once a day to control blood pressure over the 24 hour period. However, sometimes your doctor may 
recommend a lower dose of 20 mg or a higher dose of 80 mg. Tolura may also be used in combination 
with diuretics ('water tablets') such as hydrochlorothiazide which has been shown to have an additive 
blood pressure lowering effect with Tolura.

For reduction of cardiovascular events, the usual dose of Tolura is one 80 mg tablet once a day. At the 
beginning of the preventive therapy with Tolura 80 mg, blood pressure should be frequently 
monitored.

If your liver is not working properly, the usual dose should not exceed 40 mg once daily.

If you take more Tolura than you should
If you accidentally take too many tablets, contact your doctor, pharmacist, or your nearest hospital 
emergency department immediately.

If you forget to take Tolura



73

If you forget to take a dose, do not worry. Take it as soon as you remember then carry on as before. If 
you do not take your tablet on one day, take your normal dose on the next day. Do not take a double 
dose to make up for forgotten individual doses.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

Some side effects can be serious and need immediate medical attention:

You should see your doctor immediately if you experience any of the following symptoms:

Sepsis* (often called "blood poisoning", is a severe infection with whole-body inflammatory 
response), rapid swelling of the skin and mucosa (angioedema); these side effects are rare (may affect 
up to 1 in 1,000 people) but are extremely serious and patients should stop taking the medicine and see 
their doctor immediately. If these effects are not treated they could be fatal.

Possible side effects of Tolura:

Common side effects (may affect up to 1 in 10 people):
Low blood pressure (hypotension) in users treated for reduction of cardiovascular events.

Uncommon side effects (may affect up to 1 in 100 people):
Urinary tract infections, upper respiratory tract infections (e.g. sore throat, inflamed sinuses, common 
cold), deficiency in red blood cells (anaemia), high potassium levels, difficulty falling asleep, feeling 
sad (depression), fainting (syncope), feeling of spinning (vertigo), slow heart rate (bradycardia), low 
blood pressure (hypotension) in users treated for high blood pressure, dizziness on standing up 
(orthostatic hypotension), shortness of breath, cough, abdominal pain, diarrhoea, discomfort in the 
abdomen, bloating, vomiting, itching, increased sweating, drug rash, back pain, muscle cramps, 
muscle pain (myalgia), kidney impairment including acute kidney failure, pain in the chest, feeling of 
weakness, and increased level of creatinine in the blood.

Rare side effects (may affect up to 1 in 1,000 people):
Sepsis* (often called "blood poisoning", is a severe infection with whole-body inflammatory response 
which can lead to death), increase in certain white blood cells (eosinophilia), low platelet count 
(thrombocytopenia), severe allergic reaction (anaphylactic reaction), allergic reaction (e.g. rash, 
itching, difficulty breathing, wheezing, swelling of the face or low blood pressure), low blood sugar 
levels (in diabetic patients), feeling anxious, somnolence, impaired vision, fast heart beat 
(tachycardia), dry mouth, upset stomach, taste disturbance (dysgeusia), abnormal liver function 
(Japanese patients are more likely to experience these side effect), rapid swelling of the skin and 
mucosa which can also lead to death (angioedema also with fatal outcome), eczema (a skin disorder), 
redness of skin, hives (urticaria), severe drug rash, joint pain (arthralgia), pain in extremity, tendon 
pain, flu-like-illness, decreased haemoglobin (a blood protein), increased levels of uric acid, increased
hepatic enzymes or creatine phosphokinase in the blood.

Very rare side effects (may affect up to 1 in 10,000 people):
Progressive scarring of lung tissue (interstitial lung disease)**.

*The event may have happened by chance or could be related to a mechanism currently not known.

** Cases of progressive scarring of lung tissue have been reported during intake of telmisartan. 
However, it is not known whether telmisartan was the cause.

Reporting of side effects



74

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine.

5. How to store Tolura

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

Do not use this medicine after the expiry date which is stated on the carton and blister after “EXP”. 
The expiry date refers to the last day of that month.

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

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Tolura contains
- The active substance is telmisartan. Each tablet contains 80 mg telmisartan.
- The other ingredients are povidone, meglumine, sodium hydroxide, lactose monohydrate, 

sorbitol (E420) and magnesium stearate.

What Tolura looks like and contents of the pack
Tolura 80 mg tablets are white to almost white, biconvex, capsule shape tablets.

Tolura is available in blister packs containing 14, 28, 30, 56, 84, 90, 98 and 100 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

Manufacturers
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
KRKA-POLSKA Sp. z o.o., ul. Równoległa 5, 02-235 Warszawa, Poland

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

België/Belgique/Belgien
KRKA Belgium, SA.
Tél/Tel: + 32 (0) 487 50 73 62

Lietuva
UAB KRKA Lietuva
Tel: + 370 5 236 27 40

България
КРКА България ЕООД
Teл.: + 359 (02) 962 34 50

Luxembourg/Luxemburg
KRKA Belgium, SA.
Tél/Tel: + 32 (0) 487 50 73 62 (BE)

Česká republika
KRKA ČR, s.r.o.
Tel: + 420 (0) 221 115 150

Magyarország
KRKA Magyarország Kereskedelmi Kft.
Tel.: + 361 (0) 355 8490

Danmark
KRKA Sverige AB

Malta
E.J. Busuttil Ltd.



75

Tlf: + 46 (0)8 643 67 66 (SE) Tel: + 356 21 445 885

Deutschland
TAD Pharma GmbH
Tel: + 49 (0) 4721 606-0

Nederland
KRKA Belgium, SA.
Tel: + 32 (0) 487 50 73 62 (BE)

Eesti
KRKA, d.d., Novo mesto Eesti filiaal
Tel: + 372 (0) 6 671 658

Norge
KRKA Sverige AB
Tlf: + 46 (0)8 643 67 66 (SE)

Ελλάδα
QUALIA PHARMA S.A.
Τηλ: + 30 210 6256177

Österreich
KRKA Pharma GmbH, Wien
Tel: + 43 (0)1 66 24 300

España
KRKA Farmacéutica, S.L.
Tel: + 34 911 61 03 81

Polska
KRKA-POLSKA Sp. z o.o.
Tel.: + 48 (0)22 573 7500

France
KRKA France Eurl
Tél: + 33 (0)1 57 40 82 25

Portugal
KRKA Farmacêutica, Sociedade Unipessoal Lda.
Tel: + 351 (0)21 46 43 650

Hrvatska
KRKA - FARMA d.o.o.
Tel: + 385 1 6312 100

România
KRKA Romania S.R.L., Bucharest
Tel: + 4 021 310 66 05

Ireland
KRKA Pharma Dublin, Ltd.
Tel: + 353 1 293 91 80

Slovenija
KRKA, d.d., Novo mesto
Tel: + 386 (0) 1 47 51 100

Ísland
KRKA Sverige AB
Sími: + 46 (0)8 643 67 66 (SE)

Slovenská republika
KRKA Slovensko, s.r.o.
Tel: + 421 (0) 2 571 04 501

Italia
KRKA Farmaceutici Milano S.r.l.
Tel: + 39 02 3300 8841

Suomi/Finland
KRKA Finland Oy
Puh/Tel: + 358 20 754 5330

Κύπρος
Kipa Pharmacal Ltd.
Τηλ: + 357 24 651 882

Sverige
KRKA Sverige AB
Tel: + 46 (0)8 643 67 66 (SE)

Latvija
KRKA Latvija SIA
Tel: + 371 6 733 86 10

United Kingdom
Consilient Health (UK) Ltd.
Tel: + 44(0)203 751 1888

This leaflet was last revised in

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORIZATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET