ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS
1.
Telmisartan Actavis 20 mg tablets
2.
Each tablet contains 20 mg telmisartan
For a full list of excipients, see section 6.1.
3.
Tablet
White, round, flat tablets with logo T on one side.
4.
Hypertension
Treatment of essential hypertension in adults.
Cardiovascular prevention
Reduction of cardiovascular morbidity in patients with:
i) manifest atherothrombotic cardiovascular disease (history of coronary heart disease, stroke, or
peripheral arterial disease) or
ii) type 2 diabetes mellitus with documented target organ damage.
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 thiazidetype 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.
Telmisartan may be taken with or without food.
Special patient populations:
Renal impairment
:
2
No posology adjustment is required for patients with mild to moderate 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).
Hepatic impairment
:
In patients with mild to moderate hepatic impairment the posology should not exceed 40 mg once
daily (see section 4.4).
Elderly
No dose adjustment is necessary for elderly patients.
Paediatric patients
Telmisartan Actavis is not recommended for use in children below 18 years due to a lack of data on
safety and efficacy.
·
Hypersensitivity to the active substance or to any of the excipients (see section 6.1)
·
Second and third trimesters of pregnancy (see sections 4.4 and 4.6)
·
Biliary obstructive disorders
·
Severe hepatic impairment
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:
Telmisartan Actavis 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. Telmisartan Actavis
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 Telmisartan Actavis 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 Telmisartan Actavis in patients with recent kidney transplantation.
Intravascular hypovolaemia:
Symptomatic hypotension, especially after the first dose of Telmisartan Actavis, 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 Telmisartan
Actavis . Volume and/or sodium depletion should be corrected prior to administration of Telmisartan
Actavis .
Dual blockade of the renin-angiotensin-aldosterone system:
3
As a consequence of inhibiting the renin-angiotensin-aldosterone system, hypotension, syncope,
hyperkalaemia and changes in renal function (including acute renal failure) have been reported in
susceptible individuals, especially if combining medicinal products that affect this system. Dual
blockade of the renin-angiotensin-aldosterone system (e.g. by adding an ACE-inhibitor to an
angiotensin II receptor antagonist) is therefore not recommended in patients with already controlled
blood pressure and should be limited to individually defined cases with close monitoring of renal
function.
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.
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 class 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).
Ethnic differences:
As observed for angiotensin converting enzyme inhibitors, telmisartan and the other angiotensin
antagonists are apparently less effective in lowering blood pressure in black people than in non-
blacks, possibly because of higher prevalence of low-renin states in the black hypertensive population.
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
Interaction studies have only been performed in adults.
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
nonselective 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 AUC
0-24
and C
max
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
5
Other antihypertensive agents
:
The blood pressure lowering effect of telmisartan can be increased by concomitant use of other
antihypertensive medicinal products.
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.
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 Telmisartan Actavis 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 anti-hypertensive 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).
Lactation:
Because no information is available regarding the use of Telmisartan Actavis during breast-feeding,
Telmisartan Actavis is not recommended and alternative treatments with better established safety
profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.
No studies on the effects on the ability to drive and use machines have been performed. However,
when driving vehicles or operating machinery it should be taken into account that dizziness or
drowsiness may occasionally occur when taking antihypertensive therapy.
The overall incidence of adverse events reported with telmisartan (41.4%) was usually comparable to
placebo (43.9%) in placebo controlled trials in patients treated for hypertension. The incidence of
6
adverse events 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 drug 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 events and adverse events 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.
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), not known (cannot be estimated from the
available data).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Infections and infestations
Upper respiratory tract infection including pharyngitis and
sinusitis, urinary tract infection including cystitis
Sepsis including fatal outcome
1
Blood and the lymphatic system disorders
Not known:
Uncommon:
Anaemia
Rare:
Thrombocytopenia
Not known:
Eosinophilia
Immune system disorders
Rare:
Hypersensitivity
Not known:
Anaphylactic reaction
Metabolism and nutrition disorders
Uncommon:
Hyperkalaemia
Psychiatric disorders
Uncommon: Depression, insomnia
Rare: Anxiety
Nervous system disorders
Uncommon: Syncope
Eye disorders
Rare: Visual disturbance
Ear and labyrinth disorders
Uncommon: Vertigo
Cardiac disorders
Uncommon: Bradycardia
Rare: Tachycardia
Vascular disorders
Uncommon: Hypotension
2
, orthostatic hypotension
Respiratory, thoracic and mediastinal disorders
Uncommon:
Dyspnoea
7
Uncommon:
Gastrointestinal disorders
Abdominal pain, diarrhoea, dyspepsia, flatulence, vomiting
Stomach discomfort, dry mouth
Hepato-biliary disorders
Rare: Hepatic function abnormal/liver disorder
Skin and subcutaneous tissue disorders
Uncommon:
Rare:
Hyperhidrosis, pruritus, rash
Erythema, angioedema, drug eruption, toxic skin eruption, eczema
Urticaria
Muscoloskeletal and connective tissue disorders
Uncommon:
Rare:
Not known:
Myalgia back pain (e.g. sciatica), muscle spasms
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:
Not known:
Uncommon:
Chest pain, asthenia (weakness)
Influenza-like illness
Rare:
Investigations
Uncommon:
Blood creatinine increased
Blood uric acid increased, hepatic enzyme increased, blood
creatine phosphokinase increased, haemoglobin decreased
1
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
section 5.1).
2
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.
Rare:
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.
5.1 Pharmacodynamic properties
8
Rare:
Pharmacotherapeutic group: Angiotensin II Antagonists, plain, ATC Code: C09CA07.
Mechanism of action:
Telmisartan is an orally active and specific angiotensin II receptor (type AT
1
) antagonist.
Telmisartan displaces angiotensin II with very high affinity from its binding site at the AT
1
receptor
subtype, which is responsible for the known actions of angiotensin II. Telmisartan does not exhibit
any partial agonist activity at the AT
1
receptor. Telmisartan selectively binds the AT
1
receptor. The
binding is long-lasting. Telmisartan does not show affinity for other receptors, including AT
2
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.
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
(
ON
going
T
elmisartan
A
lone and in Combination with
R
amipril
G
lobal
E
ndpoint
T
rial) 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.
9
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
H
eart
O
utcomes
P
revention
E
valuation 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 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.
Beneficial effects of telmisartan on mortality and cardiovascular morbidity are currently unknown.
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 (AUC
0-∞
) 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.
10
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. C
max
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 (V
dss
) is approximately 500 l.
Metabolism:
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 (C
max
) 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 (Cl
tot
) is high (approximately 1,000 ml/min) compared with hepatic blood flow (about
1,500 ml/min).
Special Populations
Gender effects:
Gender differences in plasma concentrations were observed, C
max
and AUC being approximately
3-and 2-fold higher, respectively, in females compared to males.
Elderly patients:
The pharmacokinetics of telmisartan do not differ between the elderly and those younger than
65 years.
Patients with 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.
Patients with 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
11
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.
There is no evidence of a teratogenic effect, but animal studies indicated some hazardous potential of
telmisartan to the postnatal development of the offspring such as lower body weight, delayed eye
opening, and higher mortality.
There was no evidence of mutagenicity and relevant clastogenic activity in
in vitro
studies and no
evidence of carcinogenicity in rats and mice.
6.
6.1 List of excipients
Magnesium stearate
Croscarmellose sodium
Mannitol
Povidone
Potassium Hydroxide Pellets
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
2 years
6.4 Special precautions for storage
Al/Al blisters:
Store in the original package in order to protect from light.
HDPE tablet container with LDPE lid:
Keep the container tightly closed in order to protect from light.
6.5
Nature and contents of container
Al/Al blisters:
Pack sizes: 14 (2 x 7), 28 (4 x 7), 30 (3 x 10), 56 (8 x 7), 84 (12 x 7), 90 (9 x 10), 98 (14 x 7) or 100
(10 x 10) tablets.
HDPE container with LDPE lid and desiccant
Pack sizes: 30 or 250 tablets
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
12
7.
Actavis Group PTC ehf.
Reykjavíkurvegi 76-78
220 Hafnarfjörður
Iceland
8.
9.
Detailed information on this medicinal product is available on the website of the European Medicines
Agency
http://www.ema.europa.eu/.
13
1.
Telmisartan Actavis 40 mg tablets
2.
Each tablet contains 40 mg telmisartan
For a full list of excipients, see section 6.1.
3.
Tablet
White, oval, biconvex tablets with a break line and logo T on one side. The tablet can be divided into
equal halves.
4.
Hypertension
Treatment of essential hypertension in adults.
Cardiovascular prevention
Reduction of cardiovascular morbidity in patients with:
i) manifest atherothrombotic cardiovascular disease (history of coronary heart disease, stroke, or
peripheral arterial disease) or
ii) type 2 diabetes mellitus with documented target organ damage.
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 thiazidetype 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.
Telmisartan may be taken with or without food.
Special patient populations:
Renal impairment
:
14
No posology adjustment is required for patients with mild to moderate 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).
Hepatic impairment
:
In patients with mild to moderate hepatic impairment the posology should not exceed 40 mg once
daily (see section 4.4).
Elderly
No dose adjustment is necessary for elderly patients.
Paediatric patients
Telmisartan Actavis is not recommended for use in children below 18 years due to a lack of data on
safety and efficacy.
·
Hypersensitivity to the active substance or to any of the excipients (see section 6.1)
·
Second and third trimesters of pregnancy (see sections 4.4 and 4.6)
·
Biliary obstructive disorders
·
Severe hepatic impairment
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:
Telmisartan Actavis 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. Telmisartan Actavis
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 Telmisartan Actavis 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 Telmisartan Actavis in patients with recent kidney transplantation.
Intravascular hypovolaemia:
Symptomatic hypotension, especially after the first dose of Telmisartan Actavis, 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 Telmisartan
Actavis . Volume and/or sodium depletion should be corrected prior to administration of Telmisartan
Actavis .
Dual blockade of the renin-angiotensin-aldosterone system:
15
As a consequence of inhibiting the renin-angiotensin-aldosterone system, hypotension, syncope,
hyperkalaemia and changes in renal function (including acute renal failure) have been reported in
susceptible individuals, especially if combining medicinal products that affect this system. Dual
blockade of the renin-angiotensin-aldosterone system (e.g. by adding an ACE-inhibitor to an
angiotensin II receptor antagonist) is therefore not recommended in patients with already controlled
blood pressure and should be limited to individually defined cases with close monitoring of renal
function.
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.
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 class 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).
Ethnic differences:
As observed for angiotensin converting enzyme inhibitors, telmisartan and the other angiotensin
antagonists are apparently less effective in lowering blood pressure in black people than in non-
blacks, possibly because of higher prevalence of low-renin states in the black hypertensive population.
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.
16
Interaction studies have only been performed in adults.
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
nonselective 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 AUC
0-24
and C
max
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
17
Other antihypertensive agents
:
The blood pressure lowering effect of telmisartan can be increased by concomitant use of other
antihypertensive medicinal products.
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.
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 Telmisartan Actavis 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 anti-hypertensive 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).
Lactation:
Because no information is available regarding the use of Telmisartan Actavis during breast-feeding,
Telmisartan Actavis is not recommended and alternative treatments with better established safety
profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.
No studies on the effects on the ability to drive and use machines have been performed. However,
when driving vehicles or operating machinery it should be taken into account that dizziness or
drowsiness may occasionally occur when taking antihypertensive therapy.
The overall incidence of adverse events reported with telmisartan (41.4%) was usually comparable to
placebo (43.9%) in placebo controlled trials in patients treated for hypertension. The incidence of
18
adverse events 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 drug 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 events and adverse events 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.
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), not known (cannot be estimated from the
available data).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Infections and infestations
Upper respiratory tract infection including pharyngitis and
sinusitis, urinary tract infection including cystitis
Sepsis including fatal outcome
1
Blood and the lymphatic system disorders
Not known:
Uncommon:
Anaemia
Rare:
Thrombocytopenia
Not known:
Eosinophilia
Immune system disorders
Rare:
Hypersensitivity
Not known:
Anaphylactic reaction
Metabolism and nutrition disorders
Uncommon:
Hyperkalaemia
Psychiatric disorders
Uncommon: Depression, insomnia
Rare: Anxiety
Nervous system disorders
Uncommon: Syncope
Eye disorders
Rare: Visual disturbance
Ear and labyrinth disorders
Uncommon: Vertigo
Cardiac disorders
Uncommon: Bradycardia
Rare: Tachycardia
Vascular disorders
Uncommon: Hypotension
2
, orthostatic hypotension
Respiratory, thoracic and mediastinal disorders
Uncommon:
Dyspnoea
19
Uncommon:
Gastrointestinal disorders
Abdominal pain, diarrhoea, dyspepsia, flatulence, vomiting
Stomach discomfort, dry mouth
Hepato-biliary disorders
Rare: Hepatic function abnormal/liver disorder
Skin and subcutaneous tissue disorders
Uncommon:
Rare:
Hyperhidrosis, pruritus, rash
Erythema, angioedema, drug eruption, toxic skin eruption, eczema
Urticaria
Muscoloskeletal and connective tissue disorders
Uncommon:
Rare:
Not known:
Myalgia back pain (e.g. sciatica), muscle spasms
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:
Not known:
Uncommon:
Chest pain, asthenia (weakness)
Influenza-like illness
Rare:
Investigations
Uncommon:
Blood creatinine increased
Blood uric acid increased, hepatic enzyme increased, blood
creatine phosphokinase increased, haemoglobin decreased
1
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
section 5.1).
2
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.
Rare:
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.
5.1 Pharmacodynamic properties
20
Rare:
Pharmacotherapeutic group: Angiotensin II Antagonists, plain, ATC Code: C09CA07.
Mechanism of action:
Telmisartan is an orally active and specific angiotensin II receptor (type AT
1
) antagonist.
Telmisartan displaces angiotensin II with very high affinity from its binding site at the AT
1
receptor
subtype, which is responsible for the known actions of angiotensin II. Telmisartan does not exhibit
any partial agonist activity at the AT
1
receptor. Telmisartan selectively binds the AT
1
receptor. The
binding is long-lasting. Telmisartan does not show affinity for other receptors, including AT
2
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.
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
(
ON
going
T
elmisartan
A
lone and in Combination with
R
amipril
G
lobal
E
ndpoint
T
rial) 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.
21
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
H
eart
O
utcomes
P
revention
E
valuation 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 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.
Beneficial effects of telmisartan on mortality and cardiovascular morbidity are currently unknown.
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 (AUC
0-∞
) 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.
22
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. C
max
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 (V
dss
) is approximately 500 l.
Metabolism:
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 (C
max
) 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 (Cl
tot
) is high (approximately 1,000 ml/min) compared with hepatic blood flow (about
1,500 ml/min).
Special Populations
Gender effects:
Gender differences in plasma concentrations were observed, C
max
and AUC being approximately
3-and 2-fold higher, respectively, in females compared to males.
Elderly patients:
The pharmacokinetics of telmisartan do not differ between the elderly and those younger than
65 years.
Patients with 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.
Patients with 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
23
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.
There is no evidence of a teratogenic effect, but animal studies indicated some hazardous potential of
telmisartan to the postnatal development of the offspring such as lower body weight, delayed eye
opening, and higher mortality.
There was no evidence of mutagenicity and relevant clastogenic activity in
in vitro
studies and no
evidence of carcinogenicity in rats and mice.
6.
6.1 List of excipients
Magnesium stearate
Croscarmellose sodium
Mannitol
Povidone
Potassium Hydroxide Pellets
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
2 years
6.4 Special precautions for storage
Al/Al blisters:
Store in the original package in order to protect from light.
HDPE tablet container with LDPE lid:
Keep the container tightly closed in order to protect from light.
6.5
Nature and contents of container
Al/Al blisters:
Pack sizes: 14 (2 x 7), 28 (4 x 7), 30 (3 x 10), 56 (8 x 7), 84 (12 x 7), 90 (9 x 10), 98 (14 x 7) or 100
(10 x 10) tablets.
HDPE container with LDPE lid and desiccant
Pack sizes: 30 or 250 tablets
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
24
7.
Actavis Group PTC ehf.
Reykjavíkurvegi 76-78
220 Hafnarfjörður
Iceland
8.
9.
Detailed information on this medicinal product is available on the website of the European Medicines
Agency
http://www.ema.europa.eu/.
25
1.
Telmisartan Actavis 80 mg tablets
2.
Each tablet contains 80 mg telmisartan
For a full list of excipients, see section 6.1.
3.
Tablet
White, oval, biconvex tablets with logo T1 on one side.
4.
Hypertension
Treatment of essential hypertension in adults.
Cardiovascular prevention
Reduction of cardiovascular morbidity in patients with:
i) manifest atherothrombotic cardiovascular disease (history of coronary heart disease, stroke, or
peripheral arterial disease) or
ii) type 2 diabetes mellitus with documented target organ damage.
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 thiazidetype 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.
Telmisartan may be taken with or without food.
Special patient populations:
Renal impairment
:
26
No posology adjustment is required for patients with mild to moderate 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).
Hepatic impairment
:
In patients with mild to moderate hepatic impairment the posology should not exceed 40 mg once
daily (see section 4.4).
Elderly
No dose adjustment is necessary for elderly patients.
Paediatric patients
Telmisartan Actavis is not recommended for use in children below 18 years due to a lack of data on
safety and efficacy.
·
Hypersensitivity to the active substance or to any of the excipients (see section 6.1)
·
Second and third trimesters of pregnancy (see sections 4.4 and 4.6)
·
Biliary obstructive disorders
·
Severe hepatic impairment
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:
Telmisartan Actavis 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. Telmisartan Actavis
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 Telmisartan Actavis 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 Telmisartan Actavis in patients with recent kidney transplantation.
Intravascular hypovolaemia:
Symptomatic hypotension, especially after the first dose of Telmisartan Actavis, 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 Telmisartan
Actavis . Volume and/or sodium depletion should be corrected prior to administration of Telmisartan
Actavis .
Dual blockade of the renin-angiotensin-aldosterone system:
27
As a consequence of inhibiting the renin-angiotensin-aldosterone system, hypotension, syncope,
hyperkalaemia and changes in renal function (including acute renal failure) have been reported in
susceptible individuals, especially if combining medicinal products that affect this system. Dual
blockade of the renin-angiotensin-aldosterone system (e.g. by adding an ACE-inhibitor to an
angiotensin II receptor antagonist) is therefore not recommended in patients with already controlled
blood pressure and should be limited to individually defined cases with close monitoring of renal
function.
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.
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 class 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).
Ethnic differences:
As observed for angiotensin converting enzyme inhibitors, telmisartan and the other angiotensin
antagonists are apparently less effective in lowering blood pressure in black people than in non-
blacks, possibly because of higher prevalence of low-renin states in the black hypertensive population.
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.
28
Interaction studies have only been performed in adults.
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
nonselective 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 AUC
0-24
and C
max
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
29
Other antihypertensive agents
:
The blood pressure lowering effect of telmisartan can be increased by concomitant use of other
antihypertensive medicinal products.
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.
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 Telmisartan Actavis 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 anti-hypertensive 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).
Lactation:
Because no information is available regarding the use of Telmisartan Actavis during breast-feeding,
Telmisartan Actavis is not recommended and alternative treatments with better established safety
profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.
No studies on the effects on the ability to drive and use machines have been performed. However,
when driving vehicles or operating machinery it should be taken into account that dizziness or
drowsiness may occasionally occur when taking antihypertensive therapy.
The overall incidence of adverse events reported with telmisartan (41.4%) was usually comparable to
placebo (43.9%) in placebo controlled trials in patients treated for hypertension. The incidence of
30
adverse events 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 drug 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 events and adverse events 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.
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), not known (cannot be estimated from the
available data).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Infections and infestations
Upper respiratory tract infection including pharyngitis and
sinusitis, urinary tract infection including cystitis
Sepsis including fatal outcome
1
Blood and the lymphatic system disorders
Not known:
Uncommon:
Anaemia
Rare:
Thrombocytopenia
Not known:
Eosinophilia
Immune system disorders
Rare:
Hypersensitivity
Not known:
Anaphylactic reaction
Metabolism and nutrition disorders
Uncommon:
Hyperkalaemia
Psychiatric disorders
Uncommon: Depression, insomnia
Rare: Anxiety
Nervous system disorders
Uncommon: Syncope
Eye disorders
Rare: Visual disturbance
Ear and labyrinth disorders
Uncommon: Vertigo
Cardiac disorders
Uncommon: Bradycardia
Rare: Tachycardia
Vascular disorders
Uncommon: Hypotension
2
, orthostatic hypotension
Respiratory, thoracic and mediastinal disorders
Uncommon:
Dyspnoea
31
Uncommon:
Gastrointestinal disorders
Abdominal pain, diarrhoea, dyspepsia, flatulence, vomiting
Stomach discomfort, dry mouth
Hepato-biliary disorders
Rare: Hepatic function abnormal/liver disorder
Skin and subcutaneous tissue disorders
Uncommon:
Rare:
Hyperhidrosis, pruritus, rash
Erythema, angioedema, drug eruption, toxic skin eruption, eczema
Urticaria
Muscoloskeletal and connective tissue disorders
Uncommon:
Rare:
Not known:
Myalgia back pain (e.g. sciatica), muscle spasms
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:
Not known:
Uncommon:
Chest pain, asthenia (weakness)
Influenza-like illness
Rare:
Investigations
Uncommon:
Blood creatinine increased
Blood uric acid increased, hepatic enzyme increased, blood
creatine phosphokinase increased, haemoglobin decreased
1
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
section 5.1).
2
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.
Rare:
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.
5.1 Pharmacodynamic properties
32
Rare:
Pharmacotherapeutic group: Angiotensin II Antagonists, plain, ATC Code: C09CA07.
Mechanism of action:
Telmisartan is an orally active and specific angiotensin II receptor (type AT
1
) antagonist.
Telmisartan displaces angiotensin II with very high affinity from its binding site at the AT
1
receptor
subtype, which is responsible for the known actions of angiotensin II. Telmisartan does not exhibit
any partial agonist activity at the AT
1
receptor. Telmisartan selectively binds the AT
1
receptor. The
binding is long-lasting. Telmisartan does not show affinity for other receptors, including AT
2
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.
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
(
ON
going
T
elmisartan
A
lone and in Combination with
R
amipril
G
lobal
E
ndpoint
T
rial) 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.
33
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
H
eart
O
utcomes
P
revention
E
valuation 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 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.
Beneficial effects of telmisartan on mortality and cardiovascular morbidity are currently unknown.
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 (AUC
0-∞
) 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.
34
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. C
max
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 (V
dss
) is approximately 500 l.
Metabolism:
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 (C
max
) 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 (Cl
tot
) is high (approximately 1,000 ml/min) compared with hepatic blood flow (about
1,500 ml/min).
Special Populations
Gender effects:
Gender differences in plasma concentrations were observed, C
max
and AUC being approximately
3-and 2-fold higher, respectively, in females compared to males.
Elderly patients:
The pharmacokinetics of telmisartan do not differ between the elderly and those younger than
65 years.
Patients with 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.
Patients with 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
35
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.
There is no evidence of a teratogenic effect, but animal studies indicated some hazardous potential of
telmisartan to the postnatal development of the offspring such as lower body weight, delayed eye
opening, and higher mortality.
There was no evidence of mutagenicity and relevant clastogenic activity in
in vitro
studies and no
evidence of carcinogenicity in rats and mice.
6.
6.1 List of excipients
Magnesium stearate
Croscarmellose sodium
Mannitol
Povidone
Potassium Hydroxide Pellets
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
2 years
6.4 Special precautions for storage
Al/Al blisters:
Store in the original package in order to protect from light.
HDPE tablet container with LDPE lid:
Keep the container tightly closed in order to protect from light.
6.5
Nature and contents of container
Al/Al blisters:
Pack sizes: 14 (2 x 7), 28 (4 x 7), 30 (3 x 10), 56 (8 x 7), 84 (12 x 7), 90 (9 x 10), 98 (14 x 7) or 100
(10 x 10) tablets.
HDPE container with LDPE lid and desiccant
Pack sizes: 30 or 250 tablets
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
36
7.
Actavis Group PTC ehf.
Reykjavíkurvegi 76-78
220 Hafnarfjörður
Iceland
8.
9.
Detailed information on this medicinal product is available on the website of the European Medicines
Agency
http://www.ema.europa.eu/.
37
ANNEX II
A.
MANUFACTURING AUTHORISATION HOLDER(S)
RESPONSIBLE FOR BATCH RELEASE
B.
CONDITIONS OF THE MARKETING AUTHORISATION
38
A. MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR BATCH
RELEASE
Name and address of the manufacturer(s) responsible for batch release
Actavis hf
Reykjavíkurvegur 76-78, IS-220 Hafnarfjördur
Iceland
Actavis Ltd
BLB016 Bulebel Industrial Estate, Zejtun ZTN 3000
Malta
The printed package leaflet of the medicinal product must state the name and address of the
manufacturer responsible for the release of the concerned batch.
B. CONDITIONS OF THE MARKETING AUTHORISATION
·
Medicinal product subject to medical prescription.
·
CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND
EFFECTIVE USE OF THE MEDICINAL PRODUCT
Not applicable.
·
OTHER CONDITIONS
Pharmacovigilance system
The MAH must ensure that the system of pharmacovigilance, as described in version 5.03 dated
12 October 2009 presented in Module 1.8.1. of the Marketing Authorisation Application, is in
place and functioning before and whilst the product is on the market.
PSURs
The PSUR submission schedule should follow the PSUR schedule for the reference product Micardis.
39
ANNEX III
LABELLING AND PACKAGE LEAFLET
40
A. LABELLING
41
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
Outer carton for blister
1.
Telmisartan Actavis 20 mg tablets
telmisartan
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each tablet contains 20 mg telmisartan
3.
LIST OF EXCIPIENTS
4.
Tablets
14 tablets
28 tablets
30 tablets
56 tablets
84 tablets
90 tablets
98 tablets
100 tablets
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Read the package leaflet before use.
Oral use
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
42
9.
SPECIAL STORAGE CONDITIONS
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
Actavis Group PTC ehf.
Reykjavíkurvegi 76-78
220 Hafnarfjörður
Iceland
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Telmisartan Actavis 20 mg tablets
43
MINIMUM PARTICULARS TO APPEAR ON BLISTERS
Blister
1.
Telmisartan Actavis 20 mg tablets
telmisartan
2.
Actavis Group PTC ehf.
3.
EXPIRY DATE
EXP
4.
BATCH NUMBER
Lot
5.
OTHER
44
PARTICULARS TO APPEAR ON THE OUTER AND IMMEDIATE PACKAGING
Carton and label for tablet container
1.
Telmisartan Actavis 20 mg tablets
telmisartan
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each tablet contains 20 mg telmisartan
3.
LIST OF EXCIPIENTS
4.
Tablets
30 tablets
250 tablets
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Read the package leaflet before use.
Oral use
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
Contains desiccant, do not eat.
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Keep the container tightly closed in order to protect from light.
45
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Actavis Group PTC ehf.
Reykjavíkurvegi 76-78
220 Hafnarfjörður
Iceland
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Telmisartan Actavis 20 mg tablets
46
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
Outer carton for blister
1.
Telmisartan Actavis 40 mg tablets
telmisartan
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each tablet contains 40 mg telmisartan
3.
LIST OF EXCIPIENTS
4.
Tablets
14 tablets
28 tablets
30 tablets
56 tablets
84 tablets
90 tablets
98 tablets
100 tablets
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Read the package leaflet before use.
Oral use
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
47
9.
SPECIAL STORAGE CONDITIONS
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
Actavis Group PTC ehf.
Reykjavíkurvegi 76-78
220 Hafnarfjörður
Iceland
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Telmisartan Actavis 40 mg tablets
48
MINIMUM PARTICULARS TO APPEAR ON BLISTERS
Blister
1.
Telmisartan Actavis 40 mg tablets
telmisartan
2.
Actavis Group PTC ehf.
3.
EXPIRY DATE
EXP
4.
BATCH NUMBER
Lot
5.
OTHER
49
PARTICULARS TO APPEAR ON THE OUTER AND IMMEDIATE PACKAGING
Carton and label for tablet container
1.
Telmisartan Actavis 40 mg tablets
telmisartan
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each tablet contains 40 mg telmisartan
3.
LIST OF EXCIPIENTS
4.
Tablets
30 tablets
250 tablets
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Read the package leaflet before use.
Oral use
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
Contains desiccant, do not eat.
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Keep the container tightly closed in order to protect from light.
50
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Actavis Group PTC ehf.
Reykjavíkurvegi 76-78
220 Hafnarfjörður
Iceland
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Telmisartan Actavis 40 mg tablets
51
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
Outer carton for blister
1.
Telmisartan Actavis 80 mg tablets
telmisartan
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each tablet contains 80 mg telmisartan
3.
LIST OF EXCIPIENTS
4.
Tablets
14 tablets
28 tablets
30 tablets
56 tablets
84 tablets
90 tablets
98 tablets
100 tablets
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Read the package leaflet before use.
Oral use
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
52
9.
SPECIAL STORAGE CONDITIONS
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
Actavis Group PTC ehf.
Reykjavíkurvegi 76-78
220 Hafnarfjörður
Iceland
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Telmisartan Actavis 80 mg tablets
53
MINIMUM PARTICULARS TO APPEAR ON BLISTERS
Blister
1.
Telmisartan Actavis 80 mg tablets
telmisartan
2.
Actavis Group PTC ehf.
3.
EXPIRY DATE
EXP
4.
BATCH NUMBER
Lot
5.
OTHER
54
PARTICULARS TO APPEAR ON THE OUTER AND IMMEDIATE PACKAGING
Carton and label for tablet container
1.
Telmisartan Actavis 80 mg tablets
telmisartan
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each tablet contains 80 mg telmisartan
3.
LIST OF EXCIPIENTS
4.
Tablets
30 tablets
250 tablets
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Read the package leaflet before use.
Oral use
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
Contains desiccant, do not eat.
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Keep the container tightly closed in order to protect from light.
55
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Actavis Group PTC ehf.
Reykjavíkurvegi 76-78
220 Hafnarfjörður
Iceland
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Telmisartan Actavis 80 mg tablets
56
B. PACKAGE LEAFLET
57
PACKAGE LEAFLET: INFORMATION FOR THE USER
Telmisartan Actavis 20 mg tablets
Telmisartan
Read all of this leaflet carefully before you start taking this medicine.
-
Keep this leaflet. You may need to read it again.
-
If you have any further questions, ask your doctor or pharmacist.
-
This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even
if their symptoms are the same as yours.
-
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor or pharmacist.
In this leaflet
:
1. What Telmisartan Actavis is and what it is used for
2. Before you take Telmisartan Actavis
3. How to take Telmisartan Actavis
4. Possible side effects
5.
How to store Telmisartan Actavis
6.
Further information
1.
WHAT TELMISARTAN ACTAVIS
IS AND WHAT IT IS USED FOR
Telmisartan Actavis contains the active substance telmisartan which 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. Telmisartan Actavis blocks the effect of angiotensin II so that the
blood vessels relax, and your blood pressure is lowered.
Telmisartan Actavis tablets are 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 attacks, heart or kidney failure, strokes 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.
Telmisartan Actavis is also used to
reduce cardiovascular events (i.e. heart attack or stroke) in patients
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.
BEFORE YOU TAKE TELMISARTAN ACTAVIS
Do not take Telmisartan Actavis
-
if you are allergic to telmisartan or any other ingredients included in Telmisartan Actavis
tablets (see section Further information for a list of other ingredients).
-
If you are more than 3 months pregnant. (It is also better to avoid Telmisartan Actavis 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 any of the above applies to you, tell your doctor or pharmacist before taking Telmisartan Actavis.
58
Take special care with Telmisartan Actavis
Please tell 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.
In case of surgery or anaesthesia, you should tell your doctor that you are taking Telmisartan Actavis.
As with all other angiotensin II receptor antagonists, Telmisartan Actavis may be less effective in
lowering the blood pressure in black patients.
Children
The use of Telmisartan Actavis in children and adolescents up to the age of 18 years is not
recommended.
Taking other medicines
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines,
including medicines obtained without a prescription. 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
Telmisartan Actavis
-
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-
converting enzyme inhibitors, to treat high blood pressure), angiotensin II receptor antagonists
(to treat high blood pressure), NSAIDs (non steroidal anti-inflammatory medicines, e.g. aspirin
or ibuprofen), heparin (a medicine for thinning the blood), immunosuppressives (e.g.
cyclosporin or tacrolimus), and the antibiotic trimethoprim.
-
Diuretics ('water tablets'), especially if taken in high doses together with Telmisartan Actavis,
may lead to excessive loss of body water and low blood pressure (hypotension).
As with other blood pressure lowering medicines the effect of Telmisartan Actavis may be reduced
when you take NSAIDs (non steroidal anti-inflammatory drugs, e.g. aspirin or ibuprofen) or
corticosteroids.
Telmisartan Actavis may increase the blood pressure lowering effect of other medicines used to treat
high blood pressure.
Taking Telmisartan Actavis with food and drink
You can take Telmisartan Actavis with or without food.
Pregnancy and breast-feeding
Pregnancy
59
You must tell your doctor if you think you are (or might become) pregnant. Your doctor will normally
advise you to stop taking Telmisartan Actavis before you become pregnant or as soon as you know
you are pregnant and will advise you to take another medicine instead of Telmisartan Actavis.
Telmisartan Actavis 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. Telmisartan Actavis is not
recommended for mothers who are breast-feeding, and your doctor may choose another treatment for
you if you wish to breast-feed, especially if your baby is newborn, or was born prematurely.
Driving and using machines
No information is available on the effect of Telmisartan Actavis on the ability to drive or use
machines.
Some people feel dizzy or tired when they are treated for high blood pressure. If you feel dizzy or
tired, do not drive or use machines.
3.
HOW TO TAKE TELMISARTAN ACTAVIS
Always take Telmisartan Actavis exactly as your doctor has told you. You should check with your
doctor or pharmacist if you are not sure.
For treatment of high blood pressure, the usual dose of Telmisartan Actavis 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. Telmisartan Actavis 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 telmisartan.
For reduction of cardiovascular events, the usual dose of Telmisartan Actavis is one 80 mg tablet once
a day. At the beginning of the preventive therapy with Telmisartan Actavis 80 mg, blood pressure
should be frequently monitored.
In patients with liver problems the usual dose should not exceed 40 mg once daily.
In patients with kidney problems a lower starting dose of 20 mg is recommended.
Try to take the tablet at the same time each day. You can take Telmisartan Actavis with or without
food. The tablets should be swallowed with some water or other non-alcoholic drink. It is important
that you take Telmisartan Actavis every day until your doctor tells you otherwise. If you have the
impression that the effect of Telmisartan Actavis is too strong or too weak, talk to your doctor or
pharmacist.
If you take more Telmisartan Actavis than you should
It is important to keep to the dose as prescribed by your doctor. If you accidentally take too many
tablets ask your doctor what to do or contact your nearest hospital emergency department
immediately.
The most common symptoms of telmisartan overdose are low blood pressure (hypotension) and fast
heart beat (tachycardia). Slow heart beat (bradycardia), dizziness, higher levels of creatinine in the
blood and sudden kidney failure have also been reported.
If you forget to take Telmisartan Actavis
If you forget to take your medicine you should take the dose as soon as you remember on the same
day. 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.
60
If you stop taking Telmisartan Actavis
Take Telmisartan Actavis every day for as long as your doctor prescribes it in order to keep your
blood pressure controlled. If you have the impression that the effect of Telmisartan Actavis is too
strong or too weak, talk to your doctor or pharmacist.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, Telmisartan Actavis can cause side effects, although not everybody gets them.
These side effects may occur with certain frequencies, which are defined as follows:
-
very common: affects more than 1 user in 10
-
common: affects 1 to 10 users in 100
-
uncommon: affects 1 to 10 users in 1,000
-
rare: affects 1 to 10 users in 10,000
-
very rare: affects less than 1 user in 10,000
-
not known: frequency cannot be estimated from the available data.
Uncommon side effects include:
-
high potassium levels
-
fainting (syncope)
-
difficulty falling asleep
-
feeling of spinning (vertigo)
-
low blood pressure (hypotension) and
dizziness on standing up (orthostatic
hypotension)
-
shortness of breath
-
stomach ache
-
diarrhoea
-
upper respiratory tract infection (e.g. sore
throat, inflamed sinuses, common cold)
-
heartburn
-
bloating
-
increased sweating
-
itching
-
back pain
-
kidney problems including sudden kidney
failure
-
pain in the chest
-
vomiting
-
urinary tract infections
-
deficiency in red blood cells (anaemia)
-
rash
-
feeling sad (depression)
-
slow heart rate (bradycardia)
-
symptoms of weakness
-
increased levels of creatinine in the blood
-
muscle cramps
Rare side effects include:
-
low platelet count (thrombocytopenia)
-
feeling anxious,
-
impaired vision
-
fast heart beat (tachycardia)
-
decreased haemoglobin (a blood protein)
-
upset stomach
-
dry mouth
-
abnormal liver function
-
redness of skin
-
rapid swelling of the skin and mucosa
(angioedema)
-
flu-like illness
-
joint pain (arthralgia)
-
pain in extremity
-
increased levels of liver enzymes or
creatine phosphokinase in the blood
-
increased levels of uric acid in the blood
Side effects of unknown frequency include:
-
hives (urticaria)
-
increase in certain white blood cells
(eosinophilia)
-
allergic reaction (e.g. rash, itching,
-
inflammation of the tendons
61
difficulty breathing, wheezing, swelling of
the face or low blood pressure)
-
sepsis* (often called "blood poisoning", is
a severe infection with whole-body
inflammatory response which can lead to
death)
*In a long-term study involving more than 20,000 patients, more patients treated with telmisartan
experienced sepsis (blood poisoning) compared with patients who received no telmisartan. This may
have happened by chance or could be related to a way that telmisartan works that is currently not
known.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor or pharmacist.
5.
HOW TO STORE TELMISARTAN ACTAVIS
Keep out of the reach and sight of children.
Do not use Telmisartan Actavis after the expiry date which is stated on the carton, bottle or blister
after “EXP”. The expiry date refers to the last day of that month.
Al/Al blisters:
Store in the original package in order to protect from light.
HDPE tablet container:
Keep the container tightly closed in order to protect from light.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures will help to protect the environment.
6.
FURTHER INFORMATION
What Telmisartan Actavis contains
-
The other ingredients are magnesium stearate, croscarmellose sodium, mannitol, povidone,
potassium hydroxide pellets.
What Telmisartan Actavis looks like and contents of the pack
20 mg tablets are white, round, flat with logo T on one side
Telmisartan Actavis is provided in blister packs of 14 (2 x 7), 28 (4 x 7), 30 (3 x 10), 56 (8 x 7), 84
(12 x 7), 90 (9 x 10), 98 (14 x 7) or 100 (10 x 10) tablets and tablets containers with 30 and 250
tablets.
The tablet container contains a desiccant, do not eat the desiccant.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Actavis Group PTC ehf.
Reykjavíkurvegi 76-78
62
-
The active substance is telmisartan. Each tablet contains 20 mg telmisartan.
220 Hafnarfjörður
Iceland
Manufacturer
Actavis Hf.
Reykjavikurvegi 76-78,
IS-220 Hafnafjordur
ICELAND
Actavis Ltd.
BLB 016
Bulebel Industrial Estate
Zejtun
MALTA
For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder:
België/Belgique/Belgien
ALL-in-1 bvba
Tél/Tel: +32 (0)32 86 88 88
Luxembourg/Luxemburg
ALL-in-1 bvba
Belgique/Belgien
Tél/Tel: +32 (0)32 86 88 88
България
Актавис ЕАД
Teл.: + 359 2 9321 680
Magyarország
Actavis Hungary Kft
Tel.: +3652431-313/314
Česká republika
Actavis CZ a.s.
Tel: +420251001680
Malta
Actavis Ltd.
Tel: + 35621693533
Danmark
Actavis A/S
Tlf: +
45 72 22 30 00
Nederland
Actavis B.V.
Tel: 035 -54 299 33
Deutschland
Actavis Deutschland GmbH & Co. KG
Telefon: +49 (0)2173/1674 – 0
Norge
Actavis Norway AS
Tlf: +47 815 22 099
Eesti
UAB “Actavis Baltics” Eesti Filiaal
Tel: +372 6100 565
Österreich
Actavis GmbH
Tel: + 43 (0)662 435 235 14
Ελλάδα
PharOS - Pharmaceutical Oriented
Services Ltd
Tel : +30 210 66 64 667 – 8
Polska
Actavis Polska Sp. z o.o
Tel.: + 48 22 512 29 00
España
Actavis Spain, S.A.
Tfno.: +34 91 630 86 45
Portugal
Actavis A/S Sucursal
Tel: + 351 21 722 06 50
France
Actavis France
Tél: + 33 1 40 83 77 77
România
Actavis SRL
Tel: + 40 21 318 17 77
63
Ireland
Actavis UK Limited
United Kingdom
Tel: + 441271311234
Slovenija
Sanolabor d.d.
phone: +386 (0)1 585-4211
Ísland
Actavis Group PTC ehf
Sími: + 354-535 2326
Slovenská republika
Actavis s.r.o.
Tel: +421 2 3255 3800
Italia
Actavis Italy S.p.A.
Tel: +39 0331 583111
Suomi/Finland
Actavis Oy
Puh/Tel: +358 (0)9 348 233
Κύπρος
A. Potamitis Medicare Ltd
Τηλ: +35722583333
Sverige
Actavis AB
Tel: + 46 8 13 63 70
Latvija
Actavis Baltics pārstāvniecība Latvijā
Tel: +371 67067873
United Kingdom
Actavis UK Limited
Tel: + 441271311234
Lietuva
UAB “Actavis Baltics”
Tel: +370 5 260 9615
This leaflet was last approved in
Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu/.
64
PACKAGE LEAFLET: INFORMATION FOR THE USER
Telmisartan Actavis 40 mg tablets
Telmisartan
Read all of this leaflet carefully before you start taking this medicine.
-
Keep this leaflet. You may need to read it again.
-
If you have any further questions, ask your doctor or pharmacist.
-
This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even
if their symptoms are the same as yours.
-
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor or pharmacist.
In this leaflet
:
1. What Telmisartan Actavis is and what it is used for
2. Before you take Telmisartan Actavis
3. How to take Telmisartan Actavis
4. Possible side effects
5.
How to store Telmisartan Actavis
6.
Further information
1.
WHAT TELMISARTAN ACTAVIS
IS AND WHAT IT IS USED FOR
Telmisartan Actavis contains the active substance telmisartan which 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. Telmisartan Actavis blocks the effect of angiotensin II so that the
blood vessels relax, and your blood pressure is lowered.
Telmisartan Actavis tablets are 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 attacks, heart or kidney failure, strokes 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.
Telmisartan Actavis is also used to
reduce cardiovascular events (i.e. heart attack or stroke) in patients
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.
BEFORE YOU TAKE TELMISARTAN ACTAVIS
Do not take Telmisartan Actavis
-
if you are allergic to telmisartan or any other ingredients included in Telmisartan Actavis
tablets (see section Further information for a list of other ingredients).
-
If you are more than 3 months pregnant. (It is also better to avoid Telmisartan Actavis 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 any of the above applies to you, tell your doctor or pharmacist before taking Telmisartan Actavis.
65
Take special care with Telmisartan Actavis
Please tell 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.
In case of surgery or anaesthesia, you should tell your doctor that you are taking Telmisartan Actavis.
As with all other angiotensin II receptor antagonists, Telmisartan Actavis may be less effective in
lowering the blood pressure in black patients.
Children
The use of Telmisartan Actavis in children and adolescents up to the age of 18 years is not
recommended.
Taking other medicines
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines,
including medicines obtained without a prescription. 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
Telmisartan Actavis
-
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-
converting enzyme inhibitors, to treat high blood pressure), angiotensin II receptor antagonists
(to treat high blood pressure), NSAIDs (non steroidal anti-inflammatory medicines, e.g. aspirin
or ibuprofen), heparin (a medicine for thinning the blood), immunosuppressives (e.g.
cyclosporin or tacrolimus), and the antibiotic trimethoprim.
-
Diuretics ('water tablets'), especially if taken in high doses together with Telmisartan Actavis,
may lead to excessive loss of body water and low blood pressure (hypotension).
As with other blood pressure lowering medicines the effect of Telmisartan Actavis may be reduced
when you take NSAIDs (non steroidal anti-inflammatory drugs, e.g. aspirin or ibuprofen) or
corticosteroids.
Telmisartan Actavis may increase the blood pressure lowering effect of other medicines used to treat
high blood pressure.
Taking Telmisartan Actavis with food and drink
You can take Telmisartan Actavis with or without food.
Pregnancy and breast-feeding
Pregnancy
66
You must tell your doctor if you think you are (or might become) pregnant. Your doctor will normally
advise you to stop taking Telmisartan Actavis before you become pregnant or as soon as you know
you are pregnant and will advise you to take another medicine instead of Telmisartan Actavis.
Telmisartan Actavis 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. Telmisartan Actavis is not
recommended for mothers who are breast-feeding, and your doctor may choose another treatment for
you if you wish to breast-feed, especially if your baby is newborn, or was born prematurely.
Driving and using machines
No information is available on the effect of Telmisartan Actavis on the ability to drive or use
machines.
Some people feel dizzy or tired when they are treated for high blood pressure. If you feel dizzy or
tired, do not drive or use machines.
3.
HOW TO TAKE TELMISARTAN ACTAVIS
Always take Telmisartan Actavis exactly as your doctor has told you. You should check with your
doctor or pharmacist if you are not sure.
For treatment of high blood pressure, the usual dose of Telmisartan Actavis 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 20 mg or a higher dose of 80 mg.
Alternatively, Telmisartan Actavis may be used in combination with diuretics (‘water tablets’) such as
hydrochlorothiazide which has been shown to have an additive blood pressure lowering effect with
telmisartan.
For reduction of cardiovascular events, the usual dose of Telmisartan Actavis is one 80 mg tablet once
a day. At the beginning of the preventive therapy with Telmisartan Actavis 80 mg, blood pressure
should be frequently monitored.
In patients with liver problems the usual dose should not exceed 40 mg once daily.
In patients with kidney problems a lower starting dose of 20 mg is recommended.
Try to take the tablet at the same time each day. You can take Telmisartan Actavis with or without
food. The tablets should be swallowed with some water or other non-alcoholic drink. It is important
that you take Telmisartan Actavis every day until your doctor tells you otherwise. If you have the
impression that the effect of Telmisartan Actavis is too strong or too weak, talk to your doctor or
pharmacist.
If you take more Telmisartan Actavis than you should
It is important to keep to the dose as prescribed by your doctor. If you accidentally take too many
tablets ask your doctor what to do or contact your nearest hospital emergency department
immediately.
The most common symptoms of telmisartan overdose are low blood pressure (hypotension) and fast
heart beat (tachycardia). Slow heart beat (bradycardia), dizziness, higher levels of creatinine in the
blood and sudden kidney failure have also been reported.
If you forget to take Telmisartan Actavis
67
If you forget to take your medicine you should take the dose as soon as you remember on the same
day. 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 stop taking Telmisartan Actavis
Take Telmisartan Actavis every day for as long as your doctor prescribes it in order to keep your
blood pressure controlled. If you have the impression that the effect of Telmisartan Actavis is too
strong or too weak, talk to your doctor or pharmacist.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, Telmisartan Actavis can cause side effects, although not everybody gets them.
These side effects may occur with certain frequencies, which are defined as follows:
-
very common: affects more than 1 user in 10
-
common: affects 1 to 10 users in 100
-
uncommon: affects 1 to 10 users in 1,000
-
rare: affects 1 to 10 users in 10,000
-
very rare: affects less than 1 user in 10,000
-
not known: frequency cannot be estimated from the available data.
Uncommon side effects include:
-
high potassium levels
-
fainting (syncope)
-
difficulty falling asleep
-
feeling of spinning (vertigo)
-
low blood pressure (hypotension) and
dizziness on standing up (orthostatic
hypotension)
-
shortness of breath
-
stomach ache
-
diarrhoea
-
upper respiratory tract infection (e.g. sore
throat, inflamed sinuses, common cold)
-
heartburn
-
bloating
-
increased sweating
-
itching
-
back pain
-
kidney problems including sudden kidney
failure
-
pain in the chest
-
vomiting
-
urinary tract infections
-
deficiency in red blood cells (anaemia)
-
rash
-
feeling sad (depression)
-
slow heart rate (bradycardia)
-
symptoms of weakness
-
increased levels of creatinine in the blood
-
muscle cramps
Rare side effects include:
-
low platelet count (thrombocytopenia)
-
feeling anxious,
-
impaired vision
-
fast heart beat (tachycardia)
-
decreased haemoglobin (a blood protein)
-
upset stomach
-
dry mouth
-
abnormal liver function
-
redness of skin
-
rapid swelling of the skin and mucosa
(angioedema)
-
flu-like illness
-
joint pain (arthralgia)
-
pain in extremity
-
increased levels of liver enzymes or
creatine phosphokinase in the blood
-
increased levels of uric acid in the blood
Side effects of unknown frequency include:
68
-
hives (urticaria)
-
increase in certain white blood cells
(eosinophilia)
-
allergic reaction (e.g. rash, itching,
difficulty breathing, wheezing, swelling of
the face or low blood pressure)
-
inflammation of the tendons
-
sepsis* (often called "blood poisoning", is
a severe infection with whole-body
inflammatory response which can lead to
death)
*In a long-term study involving more than 20,000 patients, more patients treated with telmisartan
experienced sepsis (blood poisoning) compared with patients who received no telmisartan. This may
have happened by chance or could be related to a way that telmisartan works that is currently not
known.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor or pharmacist.
5.
HOW TO STORE TELMISARTAN ACTAVIS
Keep out of the reach and sight of children.
Do not use Telmisartan Actavis after the expiry date which is stated on the carton, bottle or blister
after “EXP”. The expiry date refers to the last day of that month.
Al/Al blisters:
Store in the original package in order to protect from light.
HDPE tablet container:
Keep the container tightly closed in order to protect from light.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures will help to protect the environment.
6.
FURTHER INFORMATION
What Telmisartan Actavis contains
-
The active substance is telmisartan. Each tablet contains 40 mg telmisartan.
-
The other ingredients are magnesium stearate, croscarmellose sodium, mannitol, povidone,
potassium hydroxide pellets.
What Telmisartan Actavis looks like and contents of the pack
40 mg tablets are white, oval, biconvex, with a break line and logo T on one side. The tablet can be
divided into equal halves.
Telmisartan Actavis is provided in blister packs of 14 (2 x 7), 28 (4 x 7), 30 (3 x 10), 56 (8 x 7), 84
(12 x 7), 90 (9 x 10), 98 (14 x 7) or 100 (10 x 10) tablets and tablets containers with 30 and 250
tablets.
The tablet container contains a desiccant, do not eat the desiccant.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
69
Marketing Authorisation Holder
Actavis Group PTC ehf.
Reykjavíkurvegi 76-78
220 Hafnarfjörður
Iceland
Manufacturer
Actavis Hf.
Reykjavikurvegi 76-78,
IS-220 Hafnafjordur
ICELAND
Actavis Ltd.
BLB 016
Bulebel Industrial Estate
Zejtun
MALTA
For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder:
België/Belgique/Belgien
ALL-in-1 bvba
Tél/Tel: +32 (0)32 86 88 88
Luxembourg/Luxemburg
ALL-in-1 bvba
Belgique/Belgien
Tél/Tel: +32 (0)32 86 88 88
България
Актавис ЕАД
Teл.: + 359 2 9321 680
Magyarország
Actavis Hungary Kft
Tel.: +3652431-313/314
Česká republika
Actavis CZ a.s.
Tel: +420251001680
Malta
Actavis Ltd.
Tel: + 35621693533
Danmark
Actavis A/S
Tlf: +
45 72 22 30 00
Nederland
Actavis B.V.
Tel: 035 -54 299 33
Deutschland
Actavis Deutschland GmbH & Co. KG
Telefon: +49 (0)2173/1674 – 0
Norge
Actavis Norway AS
Tlf: +47 815 22 099
Eesti
UAB “Actavis Baltics” Eesti Filiaal
Tel: +372 6100 565
Österreich
Actavis GmbH
Tel: + 43 (0)662 435 235 14
Ελλάδα
PharOS - Pharmaceutical Oriented
Services Ltd
Tel : +30 210 66 64 667 – 8
Polska
Actavis Polska Sp. z o.o
Tel.: + 48 22 512 29 00
España
Actavis Spain, S.A.
Tfno.: +34 91 630 86 45
Portugal
Actavis A/S Sucursal
Tel: + 351 21 722 06 50
70
France
Actavis France
Tél: + 33 1 40 83 77 77
România
Actavis SRL
Tel: + 40 21 318 17 77
Ireland
Actavis UK Limited
United Kingdom
Tel: + 441271311234
Slovenija
Sanolabor d.d.
phone: +386 (0)1 585-4211
Ísland
Actavis Group PTC ehf
Sími: + 354-535 2326
Slovenská republika
Actavis s.r.o.
Tel: +421 2 3255 3800
Italia
Actavis Italy S.p.A.
Tel: +39 0331 583111
Suomi/Finland
Actavis Oy
Puh/Tel: +358 (0)9 348 233
Κύπρος
A. Potamitis Medicare Ltd
Τηλ: +35722583333
Sverige
Actavis AB
Tel: + 46 8 13 63 70
Latvija
Actavis Baltics pārstāvniecība Latvijā
Tel: +371 67067873
United Kingdom
Actavis UK Limited
Tel: + 441271311234
Lietuva
UAB “Actavis Baltics”
Tel: +370 5 260 9615
This leaflet was last approved in
Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu/.
71
PACKAGE LEAFLET: INFORMATION FOR THE USER
Telmisartan Actavis 80 mg tablets
Telmisartan
Read all of this leaflet carefully before you start taking this medicine.
-
Keep this leaflet. You may need to read it again.
-
If you have any further questions, ask your doctor or pharmacist.
-
This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even
if their symptoms are the same as yours.
-
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor or pharmacist.
In this leaflet
:
1. What Telmisartan Actavis is and what it is used for
2. Before you take Telmisartan Actavis
3. How to take Telmisartan Actavis
4. Possible side effects
5.
How to store Telmisartan Actavis
6.
Further information
1.
WHAT TELMISARTAN ACTAVIS
IS AND WHAT IT IS USED FOR
Telmisartan Actavis contains the active substance telmisartan which 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. Telmisartan Actavis blocks the effect of angiotensin II so that the
blood vessels relax, and your blood pressure is lowered.
Telmisartan Actavis tablets are 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 attacks, heart or kidney failure, strokes 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.
Telmisartan Actavis is also used to
reduce cardiovascular events (i.e. heart attack or stroke) in patients
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.
BEFORE YOU TAKE TELMISARTAN ACTAVIS
Do not take Telmisartan Actavis
-
if you are allergic to telmisartan or any other ingredients included in Telmisartan Actavis
tablets (see section Further information for a list of other ingredients).
-
If you are more than 3 months pregnant. (It is also better to avoid Telmisartan Actavis 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 any of the above applies to you, tell your doctor or pharmacist before taking Telmisartan Actavis.
72
Take special care with Telmisartan Actavis
Please tell 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.
In case of surgery or anaesthesia, you should tell your doctor that you are taking Telmisartan Actavis.
As with all other angiotensin II receptor antagonists, Telmisartan Actavis may be less effective in
lowering the blood pressure in black patients.
Children
The use of Telmisartan Actavis in children and adolescents up to the age of 18 years is not
recommended.
Taking other medicines
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines,
including medicines obtained without a prescription. 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
Telmisartan Actavis
-
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-
converting enzyme inhibitors, to treat high blood pressure), angiotensin II receptor antagonists
(to treat high blood pressure), NSAIDs (non steroidal anti-inflammatory medicines, e.g. aspirin
or ibuprofen), heparin (a medicine for thinning the blood), immunosuppressives (e.g.
cyclosporin or tacrolimus), and the antibiotic trimethoprim.
-
Diuretics ('water tablets'), especially if taken in high doses together with Telmisartan Actavis,
may lead to excessive loss of body water and low blood pressure (hypotension).
As with other blood pressure lowering medicines the effect of Telmisartan Actavis may be reduced
when you take NSAIDs (non steroidal anti-inflammatory drugs, e.g. aspirin or ibuprofen) or
corticosteroids.
Telmisartan Actavis may increase the blood pressure lowering effect of other medicines used to treat
high blood pressure.
Taking Telmisartan Actavis with food and drink
You can take Telmisartan Actavis with or without food.
Pregnancy and breast-feeding
Pregnancy
73
You must tell your doctor if you think you are (or might become) pregnant. Your doctor will normally
advise you to stop taking Telmisartan Actavis before you become pregnant or as soon as you know
you are pregnant and will advise you to take another medicine instead of Telmisartan Actavis.
Telmisartan Actavis 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. Telmisartan Actavis is not
recommended for mothers who are breast-feeding, and your doctor may choose another treatment for
you if you wish to breast-feed, especially if your baby is newborn, or was born prematurely.
Driving and using machines
No information is available on the effect of Telmisartan Actavis on the ability to drive or use
machines.
Some people feel dizzy or tired when they are treated for high blood pressure. If you feel dizzy or
tired, do not drive or use machines.
3.
HOW TO TAKE TELMISARTAN ACTAVIS
Always take Telmisartan Actavis exactly as your doctor has told you. You should check with your
doctor or pharmacist if you are not sure.
For treatment of high blood pressure, the usual dose of Telmisartan Actavis 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.
Alternatively, Telmisartan Actavis may be used in combination with diuretics (‘water tablets’) such as
hydrochlorothiazide which has been shown to have an additive blood pressure lowering effect with
telmisartan.
For reduction of cardiovascular events, the usual dose of Telmisartan Actavis is one 80 mg tablet once
a day. At the beginning of the preventive therapy with Telmisartan Actavis 80 mg, blood pressure
should be frequently monitored.
In patients with liver problems the usual dose should not exceed 40 mg once daily.
In patients with kidney problems a lower starting dose of 20 mg is recommended.
Try to take the tablet at the same time each day. You can take Telmisartan Actavis with or without
food. The tablets should be swallowed with some water or other non-alcoholic drink. It is important
that you take Telmisartan Actavis every day until your doctor tells you otherwise. If you have the
impression that the effect of Telmisartan Actavis is too strong or too weak, talk to your doctor or
pharmacist.
If you take more Telmisartan Actavis than you should
It is important to keep to the dose as prescribed by your doctor. If you accidentally take too many
tablets ask your doctor what to do or contact your nearest hospital emergency department
immediately.
The most common symptoms of telmisartan overdose are low blood pressure (hypotension) and fast
heart beat (tachycardia). Slow heart beat (bradycardia), dizziness, higher levels of creatinine in the
blood and sudden kidney failure have also been reported.
If you forget to take Telmisartan Actavis
74
If you forget to take your medicine you should take the dose as soon as you remember on the same
day. 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 stop taking Telmisartan Actavis
Take Telmisartan Actavis every day for as long as your doctor prescribes it in order to keep your
blood pressure controlled. If you have the impression that the effect of Telmisartan Actavis is too
strong or too weak, talk to your doctor or pharmacist.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, Telmisartan Actavis can cause side effects, although not everybody gets them.
These side effects may occur with certain frequencies, which are defined as follows:
-
very common: affects more than 1 user in 10
-
common: affects 1 to 10 users in 100
-
uncommon: affects 1 to 10 users in 1,000
-
rare: affects 1 to 10 users in 10,000
-
very rare: affects less than 1 user in 10,000
-
not known: frequency cannot be estimated from the available data.
Uncommon side effects include:
-
high potassium levels
-
fainting (syncope)
-
difficulty falling asleep
-
feeling of spinning (vertigo)
-
low blood pressure (hypotension) and
dizziness on standing up (orthostatic
hypotension)
-
shortness of breath
-
stomach ache
-
diarrhoea
-
upper respiratory tract infection (e.g. sore
throat, inflamed sinuses, common cold)
-
heartburn
-
bloating
-
increased sweating
-
itching
-
back pain
-
kidney problems including sudden kidney
failure
-
pain in the chest
-
vomiting
-
urinary tract infections
-
deficiency in red blood cells (anaemia)
-
rash
-
feeling sad (depression)
-
slow heart rate (bradycardia)
-
symptoms of weakness
-
increased levels of creatinine in the blood
-
muscle cramps
Rare side effects include:
-
low platelet count (thrombocytopenia)
-
feeling anxious,
-
impaired vision
-
fast heart beat (tachycardia)
-
decreased haemoglobin (a blood protein)
-
upset stomach
-
dry mouth
-
abnormal liver function
-
redness of skin
-
rapid swelling of the skin and mucosa
(angioedema)
-
flu-like illness
-
joint pain (arthralgia)
-
pain in extremity
-
increased levels of liver enzymes or
creatine phosphokinase in the blood
-
increased levels of uric acid in the blood
Side effects of unknown frequency include:
75
-
hives (urticaria)
-
increase in certain white blood cells
(eosinophilia)
-
allergic reaction (e.g. rash, itching,
difficulty breathing, wheezing, swelling of
the face or low blood pressure)
-
inflammation of the tendons
-
sepsis* (often called "blood poisoning", is
a severe infection with whole-body
inflammatory response which can lead to
death)
*In a long-term study involving more than 20,000 patients, more patients treated with telmisartan
experienced sepsis (blood poisoning) compared with patients who received no telmisartan. This may
have happened by chance or could be related to a way that telmisartan works that is currently not
known.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please
tell your doctor or pharmacist.
5.
HOW TO STORE TELMISARTAN ACTAVIS
Keep out of the reach and sight of children.
Do not use Telmisartan Actavis after the expiry date which is stated on the carton, bottle or blister
after “EXP”. The expiry date refers to the last day of that month.
Al/Al blisters:
Store in the original package in order to protect from light.
HDPE tablet container:
Keep the container tightly closed in order to protect from light.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures will help to protect the environment.
6.
FURTHER INFORMATION
What Telmisartan Actavis contains
-
The active substance is telmisartan. Each tablet contains 80 mg telmisartan.
-
The other ingredients are magnesium stearate, croscarmellose sodium, mannitol, povidone,
potassium hydroxide pellets.
What Telmisartan Actavis looks like and contents of the pack
80 mg tablets are white, oval, biconvex with logo T1 on one side
Telmisartan Actavis is provided in blister packs of 14 (2 x 7), 28 (4 x 7), 30 (3 x 10), 56 (8 x 7), 84
(12 x 7), 90 (9 x 10), 98 (14 x 7) or 100 (10 x 10) tablets and tablets containers with 30 and 250
tablets.
The tablet container contains a desiccant, do not eat the desiccant.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
76
Marketing Authorisation Holder
Actavis Group PTC ehf.
Reykjavíkurvegi 76-78
220 Hafnarfjörður
Iceland
Manufacturer
Actavis Hf.
Reykjavikurvegi 76-78,
IS-220 Hafnafjordur
ICELAND
Actavis Ltd.
BLB 016
Bulebel Industrial Estate
Zejtun
MALTA
For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder:
België/Belgique/Belgien
ALL-in-1 bvba
Tél/Tel: +32 (0)32 86 88 88
Luxembourg/Luxemburg
ALL-in-1 bvba
Belgique/Belgien
Tél/Tel: +32 (0)32 86 88 88
България
Актавис ЕАД
Teл.: + 359 2 9321 680
Magyarország
Actavis Hungary Kft
Tel.: +3652431-313/314
Česká republika
Actavis CZ a.s.
Tel: +420251001680
Malta
Actavis Ltd.
Tel: + 35621693533
Danmark
Actavis A/S
Tlf: +
45 72 22 30 00
Nederland
Actavis B.V.
Tel: 035 -54 299 33
Deutschland
Actavis Deutschland GmbH & Co. KG
Telefon: +49 (0)2173/1674 – 0
Norge
Actavis Norway AS
Tlf: +47 815 22 099
Eesti
UAB “Actavis Baltics” Eesti Filiaal
Tel: +372 6100 565
Österreich
Actavis GmbH
Tel: + 43 (0)662 435 235 14
Ελλάδα
PharOS - Pharmaceutical Oriented
Services Ltd
Tel : +30 210 66 64 667 – 8
Polska
Actavis Polska Sp. z o.o
Tel.: + 48 22 512 29 00
España
Actavis Spain, S.A.
Tfno.: +34 91 630 86 45
Portugal
Actavis A/S Sucursal
Tel: + 351 21 722 06 50
77
France
Actavis France
Tél: + 33 1 40 83 77 77
România
Actavis SRL
Tel: + 40 21 318 17 77
Ireland
Actavis UK Limited
United Kingdom
Tel: + 441271311234
Slovenija
Sanolabor d.d.
phone: +386 (0)1 585-4211
Ísland
Actavis Group PTC ehf
Sími: + 354-535 2326
Slovenská republika
Actavis s.r.o.
Tel: +421 2 3255 3800
Italia
Actavis Italy S.p.A.
Tel: +39 0331 583111
Suomi/Finland
Actavis Oy
Puh/Tel: +358 (0)9 348 233
Κύπρος
A. Potamitis Medicare Ltd
Τηλ: +35722583333
Sverige
Actavis AB
Tel: + 46 8 13 63 70
Latvija
Actavis Baltics pārstāvniecība Latvijā
Tel: +371 67067873
United Kingdom
Actavis UK Limited
Tel: + 441271311234
Lietuva
UAB “Actavis Baltics”
Tel: +370 5 260 9615
This leaflet was last approved in
Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu/.
78
Source: European Medicines Agency
- Please bookmark this page (add it to your favorites).
- If you wish to link to this page, you can do so by referring to the URL address below this line.
https://theodora.com/drugs/eu/telmisartan_actavis.html
Copyright © 1995-2021 ITA all rights reserved.