Twynsta

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS



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1. NAME OF THE MEDICINAL PRODUCT

Twynsta 40 mg/5 mg tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 40 mg telmisartan and 5 mg amlodipine (as amlodipine besilate).

Excipient(s) with known effect: 
Each tablet contains 168.64 mg sorbitol (E420).
Each tablet contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Tablet

Blue and white oval shaped two layer tablets engraved with the product code A1 and the company logo 
on the white layer.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Treatment of essential hypertension in adults:

Add on therapy
Twynsta 40 mg/5 mg is indicated in adults whose blood pressure is not adequately controlled on 
amlodipine 5 mg alone.

Replacement therapy
Adult patients receiving telmisartan and amlodipine from separate tablets can instead receive tablets of 
Twynsta containing the same component doses.

4.2 Posology and method of administration

Posology
The recommended dose of this medicinal product is one tablet per day.

The maximum recommended dose is one tablet 80 mg telmisartan/10 mg amlodipine per day. This 
medicinal product is indicated for long term treatment.

Administration of amlodipine with grapefruit or grapefruit juice is not recommended as bioavailability 
may be increased in some patients resulting in increased blood pressure lowering effects (see section 
4.5).

Add on therapy
Twynsta 40 mg/5 mg may be administered in patients whose blood pressure is not adequately controlled 
with amlodipine 5 mg alone.



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Individual dose titration with the components (i.e. amlodipine and telmisartan) is recommended before
changing to the fixed dose combination. When clinically appropriate, direct change from monotherapy to 
the fixed combination may be considered.

Patients treated with 10 mg amlodipine who experience any dose limiting adverse reactions such as 
oedema, may be switched to Twynsta 40 mg/5 mg once daily, reducing the dose of amlodipine without 
reducing the overall expected antihypertensive response.

Replacement therapy
Patients receiving telmisartan and amlodipine from separate tablets can instead receive tablets of 
Twynsta containing the same component doses in one tablet once daily.

Elderly (> 65 years)
No dose adjustment is necessary for elderly patients. Little information is available in the very elderly 
patients.
Normal amlodipine dosage regimens are recommended in the elderly, but increase of dosage should take 
place with care (see section 4.4).

Renal impairment 
Limited experience is available in patients with severe renal impairment or haemodialysis. Caution is 
advised when using telmisartan/amlodipine in such patients as amlodipine and telmisartan are not 
dialysable (see also section 4.4).
No posology adjustment is required for patients with mild to moderate renal impairment.

Hepatic impairment
Twynsta is contraindicated in patients with severe hepatic impairment (see section 4.3).
In patients with mild to moderate hepatic impairment telmisartan/amlodipine should be administered with 
caution. For telmisartan the posology should not exceed 40 mg once daily (see section 4.4). 

Paediatric population
The safety and efficacy of telmisartan/amlodipine in children aged below 18 years have not been 
established. No data are available.

Method of administration
Oral use.
Twynsta can be taken with or without food. It is recommended to take Twynsta with some liquid.

4.3 Contraindications

 Hypersensitivity to the active substances, to dihydropyridine derivatives, or to any of the 
excipients listed in section 6.1

 Second and third trimesters of pregnancy (see sections 4.4 and 4.6)
 Biliary obstructive disorders and severe hepatic impairment
 Shock (including cardiogenic shock)
 Obstruction of the outflow tract of the left ventricle (e.g. high grade aortic stenosis) 
 Haemodynamically unstable heart failure after acute myocardial infarction

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



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4.4 Special warnings and precautions for use

Pregnancy
Angiotensin II receptor antagonists should not be initiated during pregnancy. Unless continued 
angiotensin II receptor antagonist therapy is considered essential, patients planning pregnancy should be 
changed to alternative antihypertensive treatments which have an established safety profile for use in 
pregnancy. When pregnancy is diagnosed, treatment with angiotensin II receptor antagonists should be 
stopped immediately, and, if appropriate, alternative therapy should be started (see section 4.3 and 4.6).

Hepatic impairment
Telmisartan is mostly eliminated in the bile. Patients with biliary obstructive disorders or hepatic 
insufficiency can be expected to have reduced clearance.
The half-life of amlodipine is prolonged and AUC values are higher in patients with impaired liver 
function; dosage recommendations have not been established. Amlodipine should therefore be initiated at 
the lower end of the dosing range and caution should be used, both on initial treatment and when 
increasing the dose. 
Telmisartan/amlodipine should therefore be used with caution in these patients.

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 (RAAS). 

Renal impairment and kidney transplantation
When telmisartan/amlodipine is used in patients with impaired renal function, a periodic monitoring of 
potassium and creatinine serum levels is recommended. There is no experience regarding the 
administration of telmisartan/amlodipine in patients with a recent kidney transplant. Telmisartan and 
amlodipine are not dialysable.

Intravascular hypovolaemia
Symptomatic hypotension, especially after the first dose, may occur in patients who are volume and/or 
sodium depleted by e.g. vigorous diuretic therapy, dietary salt restriction, diarrhoea or vomiting. Such 
conditions should be corrected before the administration of telmisartan. If hypotension occurs with 
telmisartan/amlodipine, the patient should be placed in the supine position and, if necessary, given an 
intravenous infusion of normal saline. Treatment can be continued once blood pressure has been 
stabilised.

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

Other conditions with stimulation of the renin-angiotensin-aldosterone system
In patients whose vascular tone and renal function depend predominantly on the activity of the 
renin-angiotensin-aldosterone system (e.g. patients with severe congestive heart failure or underlying 
renal disease, including renal artery stenosis), treatment with medicinal products that affect this system 
has been associated with acute hypotension, hyperazotaemia, oliguria, or rarely acute renal failure (see 
section 4.8).



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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.

Unstable angina pectoris, acute myocardial infarction
There are no data to support the use of telmisartan/amlodipine in unstable angina pectoris and during or 
within one month of a myocardial infarction.

Patients with cardiac failure
In an amlodipine long-term, placebo controlled study in patients with severe heart failure (NYHA class 
III and IV) the reported incidence of pulmonary oedema was higher in the amlodipine treated group than 
in the placebo group (see section 5.1). Therefore, patients with heart failure should be treated with 
caution.
Calcium channel blockers, including amlodipine, should be used with caution in patients with congestive 
heart failure, as they may increase the risk of future cardiovascular events and mortality.

Diabetic patients treated with insulin or antidiabetics
In these patients hypoglycaemia may occur under telmisartan treatment. Therefore, in these patients an 
appropriate blood glucose monitoring should be considered; a dose adjustment of insulin or antidiabetics 
may be required when indicated.

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

Before considering the concomitant use of medicinal products that affect the 
renin-angiotensin-aldosterone system, the benefit risk ratio should be evaluated.
The main risk factors for hyperkalaemia to be considered are:
- Diabetes mellitus, renal impairment, age (>70 years)
- Combination with one or more other medicinal products that affect the 

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

- Intercurrent events, in particular dehydration, 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, extensive trauma).

Serum potassium should be monitored closely in these patients (see section 4.5).

Elderly patients
The increase of the amlodipine dosage should take place with care in the elderly patients (see section 4.2
and 5.2).



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Other
As with any antihypertensive medicinal product, excessive reduction of blood pressure in patients with 
ischaemic cardiomyopathy or ischaemic cardiovascular disease could result in a myocardial infarction or 
stroke.

4.5 Interaction with other medicinal products and other forms of interaction

No interactions between the two components of this fixed dose combinations have been observed in 
clinical studies. 

Interactions linked to the combination
No drug interaction studies have been performed.

To be taken into account with concomitant use 

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

Medicinal products with blood pressure lowering potential
Based on their pharmacological properties it can be expected that the following medicinal products may 
potentiate the hypotensive effects of all antihypertensives including this medicinal product, e.g. baclofen, 
amifostine, neuroleptics or antidepressants. Furthermore, orthostatic hypotension may be aggravated by 
alcohol.

Corticosteroids (systemic route)
Reduction of the antihypertensive effect.

Interactions linked to telmisartan 

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. 

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



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Concomitant use requiring caution

Non-steroidal anti-inflammatory medicinal products
NSAIDs (i.e. acetylsalicylic acid at anti-inflammatory dosage regimens, COX-2 inhibitors and non-
selective NSAIDs) may reduce the antihypertensive effect of angiotensin II receptor antagonists.
In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with 
compromised renal function), the co-administration of angiotensin II receptor antagonists and medicinal 
products 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.

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

Concomitant use to be taken into account

Digoxin
When telmisartan was co-administered with digoxin, median increases in digoxin peak plasma 
concentration (49 %) and in trough concentration (20 %) were observed. When initiating, adjusting, and 
discontinuing telmisartan, monitor digoxin levels in order to maintain levels within the therapeutic range.

Interactions linked to amlodipine

Concomitant use requiring caution

CYP3A4 inhibitors
Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors (protease inhibitors, azole 
antifungals, macrolides like erythromycin or clarithromycin, verapamil or diltiazem) may give rise to 
significant increase in amlodipine exposure resulting in an increased risk of hypotension. The clinical 
translation of these PK variations may be more pronounced in the elderly. Clinical monitoring and dose 
adjustment may thus be required.

CYP3A4 inducers
Upon co-administration of known inducers of the CYP3A4, the plasma concentration of amlodipine
may vary. Therefore, blood pressure should be monitored and dose regulation considered both
during and after concomitant medication particularly with strong CYP3A4 inducers (e.g.
rifampicin, hypericum perforatum).

Dantrolene (infusion)
In animals, lethal ventricular fibrillation and cardiovascular collapse are observed in association with 
hyperkalemia after administration of verapamil and intravenous dantrolene. Due to risk of hyperkalemia, 
it is recommended that the coadministration of calcium channel blockers such as amlodipine be avoided 
in patients susceptible to malignant hyperthermia and in the management of malignant hyperthermia.

Grapefruit and grapefruit juice
Administration of Twynsta with grapefruit or grapefruit juice is not recommended since bioavailability 
may be increased in certain patients resulting in increased blood pressure lowering effects.  



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Concomitant use to be taken into account

Tacrolimus
There is a risk of increased tacrolimus blood levels when co-administered with amlodipine but the 
pharmacokinetic mechanism of this interaction is not fully understood. In order to avoid toxicity of 
tacrolimus, administration of amlodipine in a patient treated with tacrolimus requires monitoring of 
tacrolimus blood levels and dose adjustment of tacrolimus when appropriate.

Cyclosporine
No drug interaction studies have been conducted with cyclosporine and amlodipine in healthy volunteers 
or other populations with the exception of renal transplant patients, where variable trough concentration 
increases (average 0% - 40%) of cyclosporine were observed. Consideration should be given for 
monitoring cyclosporine levels in renal transplant patients on amlodipine, and cyclosporine dose 
reductions should be made as necessary.

Mechanistic Target of Rapamycin (mTOR) Inhibitors
mTOR inhibitors such as sirolimus, temsirolimus, and everolimus are CYP3A substrates. Amlodipine is a 
weak CYP3A inhibitor. With concomitant use of mTOR inhibitors, amlodipine may increase exposure of 
mTOR inhibitors.

Simvastatin
Co-administration of multiple doses of 10 mg of amlodipine with simvastatin 80 mg resulted in an 
increase in exposure to simvastatin up to 77 % compared to simvastatin alone. Therefore, the dose of 
simvastatin in patients on amlodipine should be limited to 20 mg daily.

4.6 Fertility, pregnancy and lactation

Pregnancy
There are limited data from the use of telmisartan/amlodipine in pregnant women. Animal reproductive 
toxicity studies with telmisartan/amlodipine have not been performed.

Telmisartan

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).

Studies with telmisartan 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 medicinal products. Unless continued 
angiotensin II receptor antagonist therapy is considered essential, patients planning pregnancy should be 
changed to alternative antihypertensive treatments which have an established safety profile for use in 
pregnancy. When pregnancy is diagnosed, treatment with angiotensin II receptor antagonists should be 
stopped immediately, and, if appropriate, alternative therapy should be started.

Exposure to angiotensin II receptor antagonist therapy during the second and third trimesters is known to 
induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and 
neonatal toxicity (renal failure, hypotension, hyperkalaemia) (see section 5.3).
Should exposure to angiotensin II receptor antagonists have occurred from the second trimester of 
pregnancy, ultrasound check of renal function and skull is recommended.
Infants whose mothers have taken angiotensin II receptor antagonists should be closely observed for 
hypotension (see sections 4.3 and 4.4).



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Amlodipine

The safety of amlodipine in human pregnancy has not been established.
In animal studies, reproductive toxicity was observed at high doses (see section 5.3).

Breast-feeding
Amlodipine is excreted in human milk. The proportion of the maternal dose received by the infant has 
been estimated with an interquartile range of 3 – 7%, with a maximum of 15%. The effect of amlodipine 
on infants is unknown.
Because no information is available regarding the use of telmisartan during breast-feeding, 
telmisartan/amlodipine is not recommended and alternative treatments with better established safety 
profiles during breast-feeding are preferable, especially while breast-feeding a newborn or preterm 
infant.

Fertility
No data from controlled clinical studies with the fixed dose combination or with the individual 
components are available.
Separate reproductive toxicity studies with the combination of telmisartan and amlodipine have not been 
conducted.

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

In some patients treated by calcium channel blockers, reversible biochemical changes in the head of 
spermatozoa have been reported. Clinical data are insufficient regarding the potential effect of 
amlodipine on fertility. In one rat study, adverse effects were found on male fertility (see section 5.3).

4.7 Effects on ability to drive and use machines

This medicinal product has moderate influence on the ability to drive and use machines. Patients should 
be advised that they may experience adverse reactions such as syncope, somnolence, dizziness, or vertigo 
during treatment (see section 4.8). Therefore, caution should be recommended when driving a car or 
using machines. If patients experience these adverse reactions, they should avoid potentially hazardous 
tasks such as driving or using machines.

4.8 Undesirable effects

Summary of the safety profile

The most common adverse reactions include dizziness and peripheral oedema. Serious syncope may 
occur rarely (less than 1 case per 1,000 patients).

Adverse reactions previously reported with one of the individual components (telmisartan or amlodipine) 
may be potential adverse reactions with Twynsta as well, even if not observed in clinical trials or during 
the post-marketing period.

Tabulated list of adverse reactions
The safety and tolerability of Twynsta has been evaluated in five controlled clinical studies with over 
3,500 patients, over 2,500 of whom received telmisartan in combination with amlodipine.

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.



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System Organ
Class

Twynsta Telmisartan Amlodipine

Infections and infestations
Uncommon upper respiratory tract 

infection including 
pharyngitis and
sinusitis, urinary tract 
infection including 
cystitis

Rare cystitis sepsis including fatal 
outcome1

Blood and lymphatic system disorders:
Uncommon anaemia

Rare thrombocytopenia, 
eosinophilia 

Very rare leukocytopenia, 
thrombocytopenia

Immune system disorders:
Rare hypersensitivity, 

anaphylactic reaction

Very rare hypersensitivity

Metabolism and nutrition disorders
Uncommon hyperkalaemia

Rare hypoglycaemia (in 
diabetic patients)

Very rare hyperglycaemia

Psychiatric disorders
Uncommon mood change

Rare depression,
anxiety,
insomnia

confusion

Nervous system disorders
Common dizziness

Uncommon somnolence,
migraine,
headache,
paraesthesia

Rare syncope,
peripheral neuropathy,
hypoaesthesia,
dysgeusia,
tremor



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Very rare extrapyramidal 
syndrome,
hypertonia

Eye disorders 
Common visual disturbance 

(including diplopia)
Uncommon visual impairment

Rare visual disturbance

Ear and labyrinth disorders
Uncommon vertigo tinnitus

Cardiac disorders
Uncommon bradycardia,

palpitations

Rare tachycardia

Very rare myocardial infarction, 
arrhythmia, 
ventricular 
tachycardia, atrial 
fibrillation

Vascular disorders
Uncommon hypotension,

orthostatic
hypotension, flushing

Very rare vasculitis

Respiratory, thoracic and mediastinal disorders
Uncommon cough dyspnoea dyspnoea, rhinitis

Very rare interstitial lung disease3

Gastrointestinal disorder
Common altered bowel habits 

(including diarrhoea 
and constipation)

Uncommon abdominal pain,
diarrhoea,
nausea

flatulence

Rare vomiting,
gingival hypertrophy,
dyspepsia,
dry mouth

stomach discomfort

Very rare pancreatitis, gastritis

Hepato-biliary disorders



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Rare hepatic function 
abnormal, liver 
disorder2

Very rare hepatitis, jaundice, 
hepatic enzyme 
elevations (mostly 
consistent with 
cholestasis)

Skin and subcutaneous tissue disorders
Uncommon pruritus hyperhidrosis alopecia, purpura, skin 

discolouration, 
hyperhidrosis

Rare eczema, erythema,
rash

angioedema (with fatal 
outcome), 
drug eruption, 
toxic skin eruption, 
urticaria

Very rare angioedema, 
erythema multiforme, 
urticaria, 
exfoliative dermatitis, 
Stevens-Johnson 
syndrome, 
photosensitivity

Not known toxic epidermal 
necrolysis

Musculoskeletal and connective tissue disorders
Common ankle swelling

Uncommon arthralgia,
muscle spasms
(cramps in legs),
myalgia

Rare back pain,
pain in extremity (leg
pain)

tendon pain (tendinitis 
like symptoms)

Renal and urinary disorders
Uncommon renal impairment 

including acute renal 
failure

micturition disorder, 
pollakiuria

Rare nocturia

Reproductive system and breast disorders
Uncommon erectile dysfunction gynaecomastia

General disorders and administration site condition



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Common peripheral oedema

Uncommon asthenia,
chest pain, fatigue,
oedema

pain

Rare malaise influenza-like illness

Investigations
Uncommon hepatic enzymes

increased
blood creatinine 
increased

weight increased, 
weight decreased

Rare blood uric acid
increased

blood creatine 
phosphokinase 
increased, 
haemoglobin decreased

1: the event may be a chance finding or related to a mechanism currently not known
2: most cases of hepatic function abnormal / liver disorder from post-marketing experience with 
telmisartan occurred in Japanese patients. Japanese patients are more likely to experience these adverse 
reactions.
3: cases of interstitial lung disease (predominantly interstitial pneumonia and eosinophilic pneumonia) 
have been reported from post-marketing experience with telmisartan

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

4.9 Overdose

Symptoms
Signs and symptoms of overdose are expected to be in line with exaggerated pharmacological effects. 
The most prominent manifestations of telmisartan overdose are expected to be hypotension and 
tachycardia; bradycardia, dizziness, increase in serum creatinine, and acute renal failure have also been 
reported.
Overdose with amlodipine may result in excessive peripheral vasodilatation and possibly reflex 
tachycardia. Marked and probably prolonged systemic hypotension up to and including shock with fatal 
outcome have been reported.

Treatment
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
overdose of both telmisartan and amlodipine. 
Serum electrolytes and creatinine should be monitored frequently. If hypotension occurs, the patient 
should be placed in a supine position with elevation of extremities, with salt and volume replacement 
given quickly. Supportive treatment should be instituted.
Intravenous calcium gluconate may be beneficial in reversing the effects of calcium channel blockade. 
Gastric lavage may be worthwhile in some cases. In healthy volunteers the use of charcoal up to 2 hours 
after administration of amlodipine 10 mg has been shown to reduce the absorption rate of amlodipine.
Telmisartan and Amlodipine are not removed by haemodialysis.

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


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5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Agents acting on the renin-angiotensin system, angiotensin II antagonists 
and calcium channel blockers; ATC Code: C09DB04.

Twynsta combines two antihypertensive compounds with complementary mechanisms to control blood 
pressure in patients with essential hypertension: an angiotensin II receptor antagonist, telmisartan, and a 
dihydropyridinic calcium channel blocker, amlodipine.
The combination of these substances has an additive antihypertensive effect, reducing blood pressure to a 
greater degree than either component alone.
Twynsta once daily produces effective and consistent reductions in blood pressure across the 24-hour 
therapeutic dose range.  

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

In humans, 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.

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. In this respect data concerning diastolic blood pressure 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 substances 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.

Two large randomised, controlled trials (ONTARGET (ONgoing Telmisartan Alone and in combination 
with Ramipril Global Endpoint Trial) and VA NEPHRON-D (The Veterans Affairs Nephropathy in 



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Diabetes)) have examined the use of the combination of an ACE-inhibitor with an angiotensin II receptor 
blocker.
ONTARGET was a study conducted in patients with a history of cardiovascular or cerebrovascular 
disease, or type 2 diabetes mellitus accompanied by evidence of end-organ damage. VA NEPHRON-D 
was a study in patients with type 2 diabetes mellitus and diabetic nephropathy.
These studies have shown no significant beneficial effect on renal and/or cardiovascular outcomes and 
mortality, while an increased risk of hyperkalaemia, acute kidney injury and/or hypotension as compared 
to monotherapy was observed. Given their similar pharmacodynamic properties, these results are also 
relevant for other ACE-inhibitors and angiotensin II receptor blockers.
ACE-inhibitors and angiotensin II receptor blockers should therefore not be used concomitantly in 
patients with diabetic nephropathy.

ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) was 
a study designed to test the benefit of adding aliskiren to a standard therapy of an ACE-inhibitor or an 
angiotensin II receptor blocker in patients with type 2 diabetes mellitus and chronic kidney disease, 
cardiovascular disease, or both. The study was terminated early because of an increased risk of adverse 
outcomes. Cardiovascular death and stroke were both numerically more frequent in the aliskiren group 
than in the placebo group and adverse events and serious adverse events of interest (hyperkalaemia, 
hypotension and renal dysfunction) were more frequently reported in the aliskiren group than in the 
placebo group.

Amlodipine
Amlodipine is a calcium ion influx inhibitor of the dihydropyridine group (slow channel blocker or 
calcium ion antagonist) and inhibits the transmembrane influx of calcium ions into cardiac and vascular 
smooth muscle. The mechanism of the antihypertensive action of amlodipine is due to a direct relaxant 
effect on vascular smooth muscle, leading to reductions in peripheral vascular resistance and in blood 
pressure. Experimental data indicate that amlodipine binds to both dihydropyridine and non-
dihydropyridine binding sites. Amlodipine is relatively vessel-selective, with a greater effect on vascular 
smooth muscle cells than on cardiac muscle cells.

In patients with hypertension, once daily dosing provides clinically significant reductions of blood 
pressure in both the supine and standing positions throughout the 24 hour interval. Due to the slow onset 
of action, acute hypotension is not a feature of amlodipine administration.
In hypertensive patients with normal renal function, therapeutic doses of amlodipine resulted in a 
decrease in renal vascular resistance and an increase in glomerular filtration rate and effective renal 
plasma flow, without change in filtration fraction or proteinuria.

Amlodipine has not been associated with any adverse metabolic effects or changes in plasma lipids and is 
suitable for use in patients with asthma, diabetes, and gout.

Use in patients with heart failure
Haemodynamic studies and exercise based controlled clinical trials in NYHA Class II-IV heart failure 
patients have shown that amlodipine did not lead to clinical deterioration as measured by exercise 
tolerance, left ventricular ejection fraction and clinical symptomatology.

A placebo controlled study (PRAISE) designed to evaluate patients in NYHA Class III-IV heart failure 
receiving digoxin, diuretics and ACE inhibitors has shown that amlodipine did not lead to an increase in 
risk of mortality or combined mortality and morbidity with heart failure.

In a follow-up, long term, placebo controlled study (PRAISE-2) of amlodipine in patients with 
NYHA III and IV heart failure without clinical symptoms or objective findings suggestive of underlying 
ischaemic disease, on stable doses of ACE inhibitors, digitalis, and diuretics, amlodipine had no effect on 
total cardiovascular mortality. In this same population amlodipine was associated with increased reports 
of pulmonary oedema.



16

Telmisartan/Amlodipine
In an 8-week multicenter, randomised, double-blind, placebo-controlled, parallel group factorial study in 
1461 patients with mild to severe hypertension (mean seated diastolic blood pressure ≥95 and 
≤119 mmHg), treatment with each combination dose of Twynsta resulted in significantly greater diastolic 
and systolic blood pressure reductions and higher control rates compared to the respective monotherapy 
components.

Twynsta showed dose-related reductions in systolic/diastolic blood pressure across the therapeutic dose 
range of 21.8/16.5 mmHg (40 mg/5 mg), 22.1/18.2 mmHg (80 mg/5 mg), 24.7/20.2 mmHg 
(40 mg/10 mg) and 26.4/20.1 mmHg (80 mg/10 mg). The reduction in diastolic blood pressure 
<90 mmHg was achieved in 71.6 %, 74.8 %, 82.1 %, 85.3 % of patients respectively. Values are adjusted 
for baseline and country.

The majority of the antihypertensive effect was attained within 2 weeks after initiation of therapy.
In a subset of 1050 patients with moderate to severe hypertension (DBP ≥100 mmHg) 32.7 - 51.8 %
responded sufficiently to monotherapy of either telmisartan or amlodipine. The observed mean changes 
in systolic/diastolic blood pressure with a combination therapy containing amlodipine 5 mg 
(22.2/17.2 mmHg with 40 mg/5 mg; 22.5/19.1 mmHg with 80 mg/5 mg) were comparable to or 
greater than those seen with amlodipine 10 mg (21.0/17.6 mmHg) and associated with significant 
lower oedema rates (1.4 % with 40 mg/5 mg; 0.5 % with 80 mg/5 mg; 17.6 % with amlodipine 10 mg).

Automated ambulatory blood pressure monitoring (ABPM) performed in a subset of 562 patients 
confirmed the results seen with in-clinic systolic and diastolic blood pressure reductions consistently 
over the entire 24-hours dosing period.

In a further multicentre, randomised, double-blind, active-controlled, parallel group study, a total of 1097 
patients with mild to severe hypertension who were not adequately controlled on amlodipine 5 mg 
received Twynsta (40 mg/5 mg or 80 mg/5 mg) or amlodipine alone (5 mg or 10 mg). After 8 weeks of 
treatment, each of the combinations was statistically significantly superior to both amlodipine 
monotherapy doses in reducing systolic and diastolic blood pressures (13.6/9.4 mmHg, 
15.0/10.6 mmHg with 40 mg/5 mg, 80 mg/5 mg versus 6.2/5.7 mmHg, 11.1/8.0 mmHg with 
amlodipine 5 mg and 10 mg and higher diastolic blood pressure control rates compared to the respective 
monotherapies were achieved (56.7 %, 63.8 % with 40 mg/5 mg and 80 mg/5 mg versus 42 %, 56.7 %
with amlodipine 5 mg and 10 mg). Oedema rates were significantly lower with 40 mg/5 mg and 

80 mg/5 mg compared to amlodipine 10 mg (4.4 % versus 24.9 %, respectively).

In another multicentre, randomised, double-blind, active-controlled, parallel group study, a total of 
947 patients with mild to severe hypertension who were not adequately controlled on amlodipine 10 mg 
received Twynsta (40 mg/10 mg or 80 mg/10 mg) or amlodipine alone (10 mg). After 8 weeks of 
treatment, each of the combination treatments was statistically significantly superior to amlodipine 
monotherapy in reducing diastolic and systolic blood pressure (11.1/9.2 mmHg, 11.3/ 9.3 mmHg 
with 40 mg/10 mg, 80 mg/10 mg versus 7.4/6.5 mmHg with amlodipine 10 mg) and higher diastolic 
blood pressure normalisation rates compared to monotherapy were achieved (63.7 %, 66.5 % with 
40 mg/10 mg, 80 mg/10 mg versus 51.1 % with amlodipine 10 mg).

In two corresponding open-label long-term follow up studies performed over a further 6 months the 
effect of Twynsta was maintained over the trial period. Furthermore it was shown that some patients not 
adequately controlled with Twynsta 40 mg/10 mg had additional blood pressure reduction by up-titration 
to Twynsta 80 mg/10 mg.

The overall incidence of adverse reactions with Twynsta in the clinical trial programme was low with 
only 12.7 % of patients on treatment experiencing adverse reactions. The most common adverse reactions 
were peripheral oedema and dizziness, see also section 4.8. The adverse reactions reported were in 
agreement with those anticipated from the safety profiles of the components telmisartan and amlodipine. 
No new or more severe adverse reactions were observed. The oedema related events (peripheral oedema, 



17

generalised oedema, and oedema) were consistently lower in patients who received Twynsta as compared 
to patients who received amlodipine 10 mg. In the factorial design trial the oedema rates were 1.3 % with 
Twynsta 40 mg/5 mg and 80 mg/5 mg, 8.8 % with Twynsta 40 mg/10 mg and 80 mg/10 mg and 18.4 %
with Amlodipine 10 mg. In patients not controlled on amlodipine 5 mg the oedema rates were 4.4 % for 
40 mg/5 mg and 80 mg/5 mg and 24.9 % for amlodipine 10 mg.

The antihypertensive effect of Twynsta was similar irrespective of age and gender, and was similar in 
patients with and without diabetes.

Twynsta has not been studied in any patient population other than hypertension. Telmisartan has been 
studied in a large outcome study in 25,620 patients with high cardiovascular risk (ONTARGET). 
Amlodipine has been studied in patients with chronic stable angina, vasospastic angina and 
angiographically documented coronary artery disease.

Paediatric population
The European Medicines Agency has waived the obligation to submit the results of studies with Twynsta
in all subsets of the paediatric population in hypertension (see section 4.2 for information on paediatric 
use).

5.2 Pharmacokinetic properties

Pharmacokinetic of the fixed dose combination 
The rate and extent of absorption of Twynsta are equivalent to the bioavailability of telmisartan and 
amlodipine when administered as individual tablets.

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

After oral administration of therapeutic doses, amlodipine is well absorbed with peak blood levels 
between 6-12 hours post dose. Absolute bioavailability has been estimated to be between 64 and 80 %. 
Amlodipine bioavailability is not affected by food ingestion.

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

The volume of distribution of amlodipine is approximately 21 l/kg. In vitro studies have shown that 
approximately 97.5 % of circulating amlodipine is bound to plasma proteins in hypertensive patients.

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

Amlodipine is extensively (approximatively 90 %) metabolised by the liver to inactive metabolites.

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



18

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

Amlodipine elimination from plasma is biphasic, with a terminal elimination half-life of approximately 
30 to 50 hours consistent with once daily dosing. Steady-state plasma levels are reached after continuous 
administration for 7-8 days. Ten per cent of original amlodipine and 60 % of amlodipine metabolites are 
excreted in urine. 

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

Amlodipine exhibits linear pharmacokinetics. 

Paediatric population (age below 18 years)
No pharmacokinetic data are available in the paediatric population.

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

Elderly
The pharmacokinetics of telmisartan do not differ in young and elderly patients.
The time to reach peak plasma concentrations of amlodipine is similar in elderly and younger subjects. In 
elderly patients, amlodipine clearance tends to decline with resulting increases in AUC and elimination 
half-life.

Renal impairment
In patients with mild to moderate and severe renal impairment, doubling of plasma concentrations of 
telmisartan 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 
subjects and cannot be removed by dialysis. The elimination half-life is not changed in patients with 
renal impairment. The pharmacokinetics of amlodipine are not significantly influenced by renal 
impairment.

Hepatic impairment
Pharmacokinetic studies in patients with hepatic impairment showed an increase in absolute 
bioavailability of telmisartan up to nearly 100 %. The elimination half-life of telmisartan is not changed 
in patients with hepatic impairment. Patients with hepatic insufficiency have decreased clearance of 
amlodipine with resulting increase of approximately 40-60 % in AUC.

5.3 Preclinical safety data

Since the non-clinical toxicity profiles of telmisartan and amlodipine are not overlapping, no 
exacerbation of toxicity was expected for the combination. This has been confirmed in a subchronic 
(13-week) toxicology study in rats, in which dose levels of 3.2/0.8, 10/2.5 and 40/10 mg/kg of telmisartan 
and amlodipine were tested.

Preclinical data available for the components of this fixed dose combination are reported below.

Telmisartan
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 



19

normotensive animals. In dogs, renal tubular dilation and atrophy were observed. Gastric mucosal injury 
(erosion, ulcers or inflammation) also was noted in rats and dogs. These pharmacologically-mediated 
undesirable effects, known from preclinical studies with both angiotensin converting enzyme inhibitors 
and angiotensin II receptor antagonists, were prevented by oral saline supplementation. In both species, 
increased plasma renin activity and hypertrophy/hyperplasia of the renal juxtaglomerular cells were 
observed. These changes, also a class effect of angiotensin converting enzyme inhibitors and other 
angiotensin II receptor antagonists, do not appear to have clinical significance.
No clear evidence of a teratogenic effect was observed, however at toxic dose levels of telmisartan an 
effect on the postnatal development of the offspring such as lower body weight and delayed eye opening 
was observed.
There was no evidence of mutagenicity and relevant clastogenic activity in in vitro studies and no 
evidence of carcinogenicity in rats and mice.

Amlodipine

Reproductive toxicology
Reproductive studies in rats and mice have shown delayed date of delivery, prolonged duration of labour 
and decreased pup survival at dosages approximately 50 times greater than the maximum recommended 
dosage for humans based on mg/kg.

Impairment of fertility
There was no effect on the fertility of rats treated orally with amlodipine maleate (males for 64 days and 
females for 14 days prior to mating) at doses of up to 10 mg amlodipine/kg/day (about 8 times* the 
maximum recommended human dose of 10 mg/day on an mg/m2 basis). 
In another rat study in which male rats were treated with amlodipine besilate for 30 days at a dose 
comparable with the human dose based on mg/kg, decreased plasma follicle-stimulating hormone and 
testosterone were found as well as decreases in sperm density and in the number of mature spermatids 
and Sertoli cells.

Carcinogenesis, mutagenesis
Rats and mice treated with amlodipine in the diet for two years, at concentrations calculated to provide 
daily dosage levels of 0.5, 1.25, and 2.5 mg/kg/day showed no evidence of carcinogenicity. The highest 
dose (for mice, similar to, and for rats twice* the maximum recommended clinical dose of 10 mg on a 
mg/m2 basis) was close to the maximum tolerated dose for mice but not for rats.
Mutagenicity studies revealed no drug related effects at either the gene or chromosome levels.

*Based on patient weight of 50 kg

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Colloidal anhydrous silica
Brilliant blue FCF (E133)
Ferric oxide black (E172)
Ferric oxide yellow (E172)
Magnesium stearate
Maize starch
Meglumine
Microcrystalline cellulose
Povidone K25
Pregelatinised starch (prepared from maize starch)
Sodium hydroxide
Sorbitol (E420)



20

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years

6.4 Special precautions for storage

This medicinal product does not require any special temperature storage conditions.
Store in the original package in order to protect from light and moisture.
Remove the tablets from the blister only directly prior to intake.

6.5 Nature and contents of container

Aluminium/aluminium blisters (PA/Al/PVC/Al) in a carton containing 14, 28, 56, 98 tablets or 
aluminium/aluminium perforated unit dose blisters (PA/Al/PVC/Al) in a carton containing 30 x 1, 
90 x 1 tablets and multipacks containing 360 (4 packs of 90 x 1) tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

7. MARKETING AUTHORISATION HOLDER

Boehringer Ingelheim International GmbH
Binger Str. 173
D-55216 Ingelheim am Rhein
Germany

8. MARKETING AUTHORISATION NUMBERS

EU/1/10/648/001 (14 tablets)
EU/1/10/648/002 (28 tablets)
EU/1/10/648/003 (30 x 1 tablets)
EU/1/10/648/004 (56 tablets)
EU/1/10/648/005 (90 x 1 tablets)
EU/1/10/648/006 (98 tablets)
EU/1/10/648/007 (360 (4 x 90 x 1) tablets)

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 7 October 2010
Date of latest renewal: 20 August 2015

10. DATE OF REVISION OF THE TEXT

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

http://www.emea.europa.eu


21

1. NAME OF THE MEDICINAL PRODUCT

Twynsta 40 mg/10 mg tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 40 mg telmisartan and 10 mg amlodipine (as amlodipine besilate).

Excipient(s) with known effect: 
Each tablet contains 168.64 mg sorbitol (E420).
Each tablet contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Tablet

Blue and white oval shaped two layer tablets engraved with the product code A2 and the company logo 
on the white layer.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Treatment of essential hypertension in adults:

Add on therapy
Twynsta 40 mg/10 mg is indicated in adults whose blood pressure is not adequately controlled on 
amlodipine 10 mg alone.

Replacement therapy
Adult patients receiving telmisartan and amlodipine from separate tablets can instead receive tablets of 
Twynsta containing the same component doses.

4.2 Posology and method of administration

Posology
The recommended dose of this medicinal productis one tablet per day.

The maximum recommended dose is one tablet 80 mg telmisartan/10 mg amlodipine per day. This 
medicinal product is indicated for long term treatment.

Administration of amlodipine with grapefruit or grapefruit juice is not recommended as bioavailability 
may be increased in some patients resulting in increased blood pressure lowering effects (see section 
4.5).

Add on therapy
Twynsta 40 mg/10 mg may be administered in patients whose blood pressure is not adequately controlled 
with amlodipine 10 mg alone.



22

Individual dose titration with the components (i.e. amlodipine and telmisartan) is recommended before
changing to the fixed dose combination. When clinically appropriate, direct change from monotherapy to 
the fixed combination may be considered.

Patients treated with 10 mg amlodipine who experience any dose limiting adverse reactions such as 
oedema, may be switched to Twynsta 40 mg/5 mg once daily, reducing the dose of amlodipine without 
reducing the overall expected antihypertensive response.

Replacement therapy
Patients receiving telmisartan and amlodipine from separate tablets can instead receive tablets of 
Twynsta containing the same component doses in one tablet once daily. 

Elderly (> 65 years)
No dose adjustment is necessary for elderly patients. Little information is available in the very elderly 
patients.
Normal amlodipine dosage regimens are recommended in the elderly, but increase of dosage should take 
place with care (see section 4.4).

Renal impairment 
Limited experience is available in patients with severe renal impairment or haemodialysis. Caution is 
advised when using telmisartan/amlodipine in such patients as amlodipine and telmisartan are not 
dialysable (see also section 4.4).
No posology adjustment is required for patients with mild to moderate renal impairment.

Hepatic impairment
Twynsta is contraindicated in patients with severe hepatic impairment (see section 4.3).
In patients with mild to moderate hepatic impairment telmisartan/amlodipine should be administered with 
caution. For telmisartan the posology should not exceed 40 mg once daily (see section 4.4). 

Paediatric population
The safety and efficacy of telmisartan/amlodipine in children aged below 18 years have not been 
established. No data are available.

Method of administration
Oral use.
Twynsta can be taken with or without food. It is recommended to take Twynsta with some liquid.

4.3 Contraindications

 Hypersensitivity to the active substances, to dihydropyridine derivatives, or to any of the 
excipients listed in section 6.1

 Second and third trimesters of pregnancy (see sections 4.4 and 4.6)
 Biliary obstructive disorders and severe hepatic impairment
 Shock (including cardiogenic shock)
 Obstruction of the outflow tract of the left ventricle (e.g. high grade aortic stenosis) 
 Haemodynamically unstable heart failure after acute myocardial infarction

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



23

4.4 Special warnings and precautions for use

Pregnancy
Angiotensin II receptor antagonists should not be initiated during pregnancy. Unless continued 
angiotensin II receptor antagonist therapy is considered essential, patients planning pregnancy should be 
changed to alternative antihypertensive treatments which have an established safety profile for use in 
pregnancy. When pregnancy is diagnosed, treatment with angiotensin II receptor antagonists should be 
stopped immediately, and, if appropriate, alternative therapy should be started (see section 4.3 and 4.6).

Hepatic impairment
Telmisartan is mostly eliminated in the bile. Patients with biliary obstructive disorders or hepatic 
insufficiency can be expected to have reduced clearance. 
The half-life of amlodipine is prolonged and AUC values are higher in patients with impaired liver 
function; dosage recommendations have not been established. Amlodipine should therefore be initiated at 
the lower end of the dosing range and caution should be used, both on initial treatment and when 
increasing the dose. 
Telmisartan/amlodipine should therefore be used with caution in these patients.

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 (RAAS). 

Renal impairment and kidney transplantation
When telmisartan/amlodipine is used in patients with impaired renal function, a periodic monitoring of 
potassium and creatinine serum levels is recommended. There is no experience regarding the 
administration of telmisartan/amlodipine in patients with a recent kidney transplant. Telmisartan and 
amlodipine are not dialysable.

Intravascular hypovolaemia
Symptomatic hypotension, especially after the first dose, may occur in patients who are volume and/or 
sodium depleted by e.g. vigorous diuretic therapy, dietary salt restriction, diarrhoea or vomiting. Such 
conditions should be corrected before the administration of telmisartan. If hypotension occurs 
withtelmisartan/amlodipine, the patient should be placed in the supine position and, if necessary, given 
an intravenous infusion of normal saline. Treatment can be continued once blood pressure has been 
stabilised.

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

Other conditions with stimulation of the renin-angiotensin-aldosterone system
In patients whose vascular tone and renal function depend predominantly on the activity of the 
renin-angiotensin-aldosterone system (e.g. patients with severe congestive heart failure or underlying 
renal disease, including renal artery stenosis), treatment with medicinal products that affect this system 
has been associated with acute hypotension, hyperazotaemia, oliguria, or rarely acute renal failure (see 
section 4.8).



24

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.

Unstable angina pectoris, acute myocardial infarction
There are no data to support the use of telmisartan/amlodipine in unstable angina pectoris and during or 
within one month of a myocardial infarction.

Patients with cardiac failure
In an amlodipine long-term, placebo controlled study in patients with severe heart failure (NYHA class 
III and IV) the reported incidence of pulmonary oedema was higher in the amlodipine treated group than 
in the placebo group (see section 5.1). Therefore, patients with heart failure should be treated with 
caution.
Calcium channel blockers, including amlodipine, should be used with caution in patients with congestive 
heart failure, as they may increase the risk of future cardiovascular events and mortality.

Diabetic patients treated with insulin or antidiabetics
In these patients hypoglycaemia may occur under telmisartan treatment. Therefore, in these patients an 
appropriate blood glucose monitoring should be considered; a dose adjustment of insulin or antidiabetics 
may be required when indicated.

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

Before considering the concomitant use of medicinal products that affect the 
renin-angiotensin-aldosterone system, the benefit risk ratio should be evaluated.
The main risk factors for hyperkalaemia to be considered are:
- Diabetes mellitus, renal impairment, age (>70 years)
- Combination with one or more other medicinal products that affect the 

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

- Intercurrent events, in particular dehydration, 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, extensive trauma).

Serum potassium should be monitored closely in these patients (see section 4.5).

Elderly patients
The increase of the amlodipine dosage should take place with care in the elderly patients (see section 4.2
and 5.2).



25

Other
As with any antihypertensive medicinal product, excessive reduction of blood pressure in patients with 
ischaemic cardiomyopathy or ischaemic cardiovascular disease could result in a myocardial infarction or 
stroke.

4.5 Interaction with other medicinal products and other forms of interaction

No interactions between the two components of this fixed dose combinations have been observed in 
clinical studies. 

Interactions linked to the combination
No drug interaction studies have been performed.

To be taken into account with concomitant use 

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

Medicinal products with blood pressure lowering potential
Based on their pharmacological properties it can be expected that the following medicinal products may 
potentiate the hypotensive effects of all antihypertensives including this medicinal product, e.g. baclofen, 
amifostine, neuroleptics or antidepressants. Furthermore, orthostatic hypotension may be aggravated by 
alcohol.

Corticosteroids (systemic route)
Reduction of the antihypertensive effect.

Interactions linked to telmisartan 

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. 

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



26

Concomitant use requiring caution

Non-steroidal anti-inflammatory medicinal products
NSAIDs (i.e. acetylsalicylic acid at anti-inflammatory dosage regimens, COX-2 inhibitors and non-
selective NSAIDs) may reduce the antihypertensive effect of angiotensin II receptor antagonists.
In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with 
compromised renal function), the co-administration of angiotensin II receptor antagonists and medicinal 
products 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.

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

Concomitant use to be taken into account

Digoxin
When telmisartan was co-administered with digoxin, median increases in digoxin peak plasma 
concentration (49 %) and in trough concentration (20 %) were observed. When initiating, adjusting, and 
discontinuing telmisartan, monitor digoxin levels in order to maintain levels within the therapeutic range.

Interactions linked to amlodipine

Concomitant use requiring caution

CYP3A4 inhibitors
Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors (protease inhibitors, azole 
antifungals, macrolides like erythromycin or clarithromycin, verapamil or diltiazem) may give rise to 
significant increase in amlodipine exposure resulting in an increased risk of hypotension. The clinical 
translation of these PK variations may be more pronounced in the elderly. Clinical monitoring and dose 
adjustment may thus be required.

CYP3A4 inducers
Upon co-administration of known inducers of the CYP3A4, the plasma concentration of amlodipine
may vary. Therefore, blood pressure should be monitored and dose regulation considered both
during and after concomitant medication particularly with strong CYP3A4 inducers (e.g.
rifampicin, hypericum perforatum).

Dantrolene (infusion)
In animals, lethal ventricular fibrillation and cardiovascular collapse are observed in association with 
hyperkalemia after administration of verapamil and intravenous dantrolene. Due to risk of hyperkalemia, 
it is recommended that the coadministration of calcium channel blockers such as amlodipine be avoided 
in patients susceptible to malignant hyperthermia and in the management of malignant hyperthermia.

Grapefruit and grapefruit juice
Administration of Twynsta with grapefruit or grapefruit juice is not recommended since bioavailability 
may be increased in certain patients resulting in increased blood pressure lowering effects.  



27

Concomitant use to be taken into account

Tacrolimus
There is a risk of increased tacrolimus blood levels when co-administered with amlodipine but the 
pharmacokinetic mechanism of this interaction is not fully understood. In order to avoid toxicity of 
tacrolimus, administration of amlodipine in a patient treated with tacrolimus requires monitoring of 
tacrolimus blood levels and dose adjustment of tacrolimus when appropriate.

Cyclosporine
No drug interaction studies have been conducted with cyclosporine and amlodipine in healthy volunteers 
or other populations with the exception of renal transplant patients, where variable trough concentration 
increases (average 0% - 40%) of cyclosporine were observed. Consideration should be given for 
monitoring cyclosporine levels in renal transplant patients on amlodipine, and cyclosporine dose 
reductions should be made as necessary.

Mechanistic Target of Rapamycin (mTOR) Inhibitors
mTOR inhibitors such as sirolimus, temsirolimus, and everolimus are CYP3A substrates. Amlodipine is a 
weak CYP3A inhibitor. With concomitant use of mTOR inhibitors, amlodipine may increase exposure of 
mTOR inhibitors.

Simvastatin
Co-administration of multiple doses of 10 mg of amlodipine with simvastatin 80 mg resulted in an 
increase in exposure to simvastatin up to 77 % compared to simvastatin alone. Therefore, the dose of 
simvastatin in patients on amlodipine should be limited to 20 mg daily.

4.6 Fertility, pregnancy and lactation

Pregnancy
There are limited data from the use of telmisartan/amlodipine in pregnant women. Animal reproductive 
toxicity studies with telmisartan/amlodipine have not been performed.

Telmisartan

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).

Studies with telmisartan 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 medicinal products. Unless continued angiotensin II 
receptor antagonist therapy is considered essential, patients planning pregnancy should be changed to 
alternative antihypertensive treatments which have an established safety profile for use in pregnancy. 
When pregnancy is diagnosed, treatment with angiotensin II receptor antagonists should be stopped 
immediately, and, if appropriate, alternative therapy should be started.

Exposure to angiotensin II receptor antagonist therapy during the second and third trimesters is known to 
induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and 
neonatal toxicity (renal failure, hypotension, hyperkalaemia) (see section 5.3).
Should exposure to angiotensin II receptor antagonists have occurred from the second trimester of 
pregnancy, ultrasound check of renal function and skull is recommended.
Infants whose mothers have taken angiotensin II receptor antagonists should be closely observed for 
hypotension (see sections 4.3 and 4.4).



28

Amlodipine

The safety of amlodipine in human pregnancy has not been established.
In animal studies, reproductive toxicity was observed at high doses (see section 5.3).

Breast-feeding
Amlodipine is excreted in human milk. The proportion of the maternal dose received by the infant has 
been estimated with an interquartile range of 3 – 7%, with a maximum of 15%. The effect of amlodipine 
on infants is unknown.
Because no information is available regarding the use of telmisartan during breast-feeding, 
telmisartan/amlodipine is not recommended and alternative treatments with better established safety 
profiles during breast-feeding are preferable, especially while breast-feeding a newborn or preterm 
infant.

Fertility
No data from controlled clinical studies with the fixed dose combination or with the individual 
components are available.

Separate reproductive toxicity studies with the combination of telmisartan and amlodipine have not been 
conducted.
In preclinical studies, no effects of telmisartan on male and female fertility were observed.

In some patients treated by calcium channel blockers, reversible biochemical changes in the head of 
spermatozoa have been reported. Clinical data are insufficient regarding the potential effect of 
amlodipine on fertility. In one rat study, adverse effects were found on male fertility (see section 5.3).

4.7 Effects on ability to drive and use machines

This medicinal product has moderate influence on the ability to drive and use machines. Patients should 
be advised that they may experience adverse reactions such as syncope, somnolence, dizziness, or vertigo 
during treatment (see section 4.8). Therefore, caution should be recommended when driving a car or 
using machines. If patients experience these adverse reactions, they should avoid potentially hazardous 
tasks such as driving or using machines.

4.8 Undesirable effects

Summary of the safety profile

The most common adverse reactions include dizziness and peripheral oedema. Serious syncope may 
occur rarely (less than 1 case per 1,000 patients).

Adverse reactions previously reported with one of the individual components (telmisartan or amlodipine) 
may be potential adverse reactions with Twynsta as well, even if not observed in clinical trials or during 
the post-marketing period.

Tabulated list of adverse reactions
The safety and tolerability of Twynsta has been evaluated in five controlled clinical studies with over 
3,500 patients, over 2,500 of whom received telmisartan in combination with amlodipine.

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.



29

System Organ
Class

Twynsta Telmisartan Amlodipine

Infections and infestations
Uncommon upper respiratory tract 

infection including 
pharyngitis and
sinusitis, urinary tract 
infection including 
cystitis

Rare cystitis sepsis including fatal 
outcome1

Blood and lymphatic system disorders:
Uncommon anaemia

Rare thrombocytopenia, 
eosinophilia 

Very rare leukocytopenia, 
thrombocytopenia

Immune system disorders:
Rare hypersensitivity, 

anaphylactic reaction

Very rare hypersensitivity

Metabolism and nutrition disorders
Uncommon hyperkalaemia

Rare hypoglycaemia (in 
diabetic patients)

Very rare hyperglycaemia

Psychiatric disorders
Uncommon mood change

Rare depression,
anxiety,
insomnia

confusion

Nervous system disorders
Common dizziness

Uncommon somnolence,
migraine,
headache,
paraesthesia

Rare syncope,
peripheral neuropathy,
hypoaesthesia,
dysgeusia,
tremor



30

Very rare extrapyramidal 
syndrome,
hypertonia

Eye disorders 
Common visual disturbance 

(including diplopia)
Uncommon visual impairment

Rare visual disturbance

Ear and labyrinth disorders
Uncommon vertigo tinnitus

Cardiac disorders
Uncommon bradycardia,

palpitations

Rare tachycardia

Very rare myocardial infarction, 
arrhythmia, 
ventricular 
tachycardia, atrial 
fibrillation

Vascular disorders
Uncommon hypotension,

orthostatic
hypotension, flushing

Very rare vasculitis

Respiratory, thoracic and mediastinal disorders
Uncommon cough dyspnoea dyspnoea, rhinitis

Very rare interstitial lung disease3

Gastrointestinal disorder
Common altered bowel habits 

(including diarrhoea 
and constipation)

Uncommon abdominal pain,
diarrhoea,
nausea

flatulence

Rare vomiting,
gingival hypertrophy,
dyspepsia,
dry mouth

stomach discomfort

Very rare pancreatitis, gastritis

Hepato-biliary disorders



31

Rare hepatic function 
abnormal, liver 
disorder2

Very rare hepatitis, jaundice, 
hepatic enzyme 
elevations (mostly 
consistent with 
cholestasis)

Skin and subcutaneous tissue disorders
Uncommon pruritus hyperhidrosis alopecia, purpura, skin 

discolouration, 
hyperhidrosis

Rare eczema, erythema,
rash

angioedema (with fatal 
outcome), 
drug eruption, 
toxic skin eruption, 
urticaria

Very rare angioedema, 
erythema multiforme, 
urticaria, 
exfoliative dermatitis, 
Stevens-Johnson 
syndrome, 
photosensitivity

Not known toxic epidermal 
necrolysis

Musculoskeletal and connective tissue disorders
Common ankle swelling

Uncommon arthralgia,
muscle spasms
(cramps in legs),
myalgia

Rare back pain,
pain in extremity (leg
pain)

tendon pain (tendinitis 
like symptoms)

Renal and urinary disorders
Uncommon renal impairment 

including acute renal 
failure

micturition disorder, 
pollakiuria

Rare nocturia

Reproductive system and breast disorders
Uncommon erectile dysfunction gynaecomastia

General disorders and administration site condition
Common peripheral oedema



32

Uncommon asthenia,
chest pain, fatigue,
oedema

pain

Rare malaise influenza-like illness

Investigations
Uncommon hepatic enzymes

increased
blood creatinine 
increased

weight increased, 
weight decreased

Rare blood uric acid
increased

blood creatine 
phosphokinase 
increased, 
haemoglobin decreased

1: the event may be a chance finding or related to a mechanism currently not known
2: most cases of hepatic function abnormal / liver disorder from post-marketing experience with 
telmisartan occurred in Japanese patients. Japanese patients are more likely to experience these adverse 
reactions.
3: cases of interstitial lung disease (predominantly interstitial pneumonia and eosinophilic pneumonia) 
have been reported from post-marketing experience with telmisartan

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

4.9 Overdose

Symptoms
Signs and symptoms of overdose are expected to be in line with exaggerated pharmacological effects. 
The most prominent manifestations of telmisartan overdose are expected to be hypotension and 
tachycardia; bradycardia, dizziness, increase in serum creatinine, and acute renal failure have also been 
reported.
Overdose with amlodipine may result in excessive peripheral vasodilatation and possibly reflex 
tachycardia. Marked and probably prolonged systemic hypotension up to and including shock with fatal 
outcome have been reported.

Treatment
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
overdose of both telmisartan and amlodipine. 
Serum electrolytes and creatinine should be monitored frequently. If hypotension occurs, the patient 
should be placed in a supine position with elevation of extremities, with salt and volume replacement 
given quickly. Supportive treatment should be instituted. 
Intravenous calcium gluconate may be beneficial in reversing the effects of calcium channel blockade. 
Gastric lavage may be worthwhile in some cases. In healthy volunteers the use of charcoal up to 2 hours 
after administration of amlodipine 10 mg has been shown to reduce the absorption rate of amlodipine.
Telmisartan and Amlodipine are not removed by haemodialysis.

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


33

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Agents acting on the renin-angiotensin system, angiotensin II antagonists 
and calcium channel blockers; ATC Code: C09DB04.

Twynsta combines two antihypertensive compounds with complementary mechanisms to control blood 
pressure in patients with essential hypertension: an angiotensin II receptor antagonist, telmisartan, and a 
dihydropyridinic calcium channel blocker, amlodipine.
The combination of these substances has an additive antihypertensive effect, reducing blood pressure to a 
greater degree than either component alone.
Twynsta once daily produces effective and consistent reductions in blood pressure across the 24-hour 
therapeutic dose range.  

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

In humans, 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.

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. In this respect data concerning diastolic blood pressure 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 substances 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.

Two large randomised, controlled trials (ONTARGET (ONgoing Telmisartan Alone and in combination 
with Ramipril Global Endpoint Trial) and VA NEPHRON-D (The Veterans Affairs Nephropathy in 



34

Diabetes)) have examined the use of the combination of an ACE-inhibitor with an angiotensin II receptor 
blocker.
ONTARGET was a study conducted in patients with a history of cardiovascular or cerebrovascular 
disease, or type 2 diabetes mellitus accompanied by evidence of end-organ damage. VA NEPHRON-D 
was a study in patients with type 2 diabetes mellitus and diabetic nephropathy.
These studies have shown no significant beneficial effect on renal and/or cardiovascular outcomes and 
mortality, while an increased risk of hyperkalaemia, acute kidney injury and/or hypotension as compared 
to monotherapy was observed. Given their similar pharmacodynamic properties, these results are also 
relevant for other ACE-inhibitors and angiotensin II receptor blockers.
ACE-inhibitors and angiotensin II receptor blockers should therefore not be used concomitantly in 
patients with diabetic nephropathy.

ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) was 
a study designed to test the benefit of adding aliskiren to a standard therapy of an ACE-inhibitor or an 
angiotensin II receptor blocker in patients with type 2 diabetes mellitus and chronic kidney disease, 
cardiovascular disease, or both. The study was terminated early because of an increased risk of adverse
outcomes. Cardiovascular death and stroke were both numerically more frequent in the aliskiren group 
than in the placebo group and adverse events and serious adverse events of interest (hyperkalaemia, 
hypotension and renal dysfunction) were more frequently reported in the aliskiren group than in the 
placebo group.

Amlodipine
Amlodipine is a calcium ion influx inhibitor of the dihydropyridine group (slow channel blocker or 
calcium ion antagonist) and inhibits the transmembrane influx of calcium ions into cardiac and vascular 
smooth muscle. The mechanism of the antihypertensive action of amlodipine is due to a direct relaxant 
effect on vascular smooth muscle, leading to reductions in peripheral vascular resistance and in blood 
pressure. Experimental data indicate that amlodipine binds to both dihydropyridine and non-
dihydropyridine binding sites. Amlodipine is relatively vessel-selective, with a greater effect on vascular 
smooth muscle cells than on cardiac muscle cells.

In patients with hypertension, once daily dosing provides clinically significant reductions of blood 
pressure in both the supine and standing positions throughout the 24 hour interval. Due to the slow onset 
of action, acute hypotension is not a feature of amlodipine administration.
In hypertensive patients with normal renal function, therapeutic doses of amlodipine resulted in a 
decrease in renal vascular resistance and an increase in glomerular filtration rate and effective renal 
plasma flow, without change in filtration fraction or proteinuria.

Amlodipine has not been associated with any adverse metabolic effects or changes in plasma lipids and is 
suitable for use in patients with asthma, diabetes, and gout.

Use in patients with heart failure
Haemodynamic studies and exercise based controlled clinical trials in NYHA Class II-IV heart failure 
patients have shown that amlodipine did not lead to clinical deterioration as measured by exercise 
tolerance, left ventricular ejection fraction and clinical symptomatology.

A placebo controlled study (PRAISE) designed to evaluate patients in NYHA Class III-IV heart failure 
receiving digoxin, diuretics and ACE inhibitors has shown that amlodipine did not lead to an increase in 
risk of mortality or combined mortality and morbidity with heart failure.

In a follow-up, long term, placebo controlled study (PRAISE-2) of amlodipine in patients with NYHA III 
and IV heart failure without clinical symptoms or objective findings suggestive of underlying ischaemic 
disease, on stable doses of ACE inhibitors, digitalis, and diuretics, amlodipine had no effect on total 
cardiovascular mortality. In this same population amlodipine was associated with increased reports of 
pulmonary oedema.



35

Telmisartan/Amlodipine
In an 8-week multicenter, randomised, double-blind, placebo-controlled, parallel group factorial study in 
1461 patients with mild to severe hypertension (mean seated diastolic blood pressure ≥95 and 
≤119 mmHg), treatment with each combination dose of Twynsta resulted in significantly greater diastolic 
and systolic blood pressure reductions and higher control rates compared to the respective monotherapy 
components.

Twynsta showed dose-related reductions in systolic/diastolic blood pressure across the therapeutic dose 
range of 21.8/16.5 mmHg (40 mg/5 mg), 22.1/18.2 mmHg (80 mg/5 mg), 24.7/20.2 mmHg 
(40 mg/10 mg) and 26.4/20.1 mmHg (80 mg/10 mg). The reduction in diastolic blood pressure 
<90 mmHg was achieved in 71.6 %, 74.8 %, 82.1 %, 85.3 % of patients respectively. Values are adjusted 
for baseline and country.

The majority of the antihypertensive effect was attained within 2 weeks after initiation of therapy.
In a subset of 1050 patients with moderate to severe hypertension (DBP ≥100 mmHg) 32.7 – 51.8 %
responded sufficiently to monotherapy of either telmisartan or amlodipine. The observed mean changes 
in systolic/diastolic blood pressure with a combination therapy containing amlodipine 5 mg 
(22.2/17.2 mmHg with 40 mg/5 mg; 22.5/19.1 mmHg with 80 mg/5 mg) were comparable to or 
greater than those seen with amlodipine 10 mg (21.0/17.6 mmHg) and associated with significant 
lower oedema rates (1.4 % with 40 mg/5 mg; 0.5 % with 80 mg/5 mg; 17.6 % with amlodipine 10 mg).

Automated ambulatory blood pressure monitoring (ABPM) performed in a subset of 562 patients 
confirmed the results seen with in-clinic systolic and diastolic blood pressure reductions consistently 
over the entire 24-hours dosing period.

In a further multicentre, randomised, double-blind, active-controlled, parallel group study, a total of 1097
patients with mild to severe hypertension who were not adequately controlled on amlodipine 5 mg 
received Twynsta (40 mg/5 mg or 80 mg/5 mg) or amlodipine alone (5 mg or 10 mg). After 8 weeks of 
treatment, each of the combinations was statistically significantly superior to both amlodipine 
monotherapy doses in reducing systolic and diastolic blood pressures (13.6/9.4 mmHg, 
15.0/10.6 mmHg with 40 mg/5 mg, 80 mg/5 mg versus 6.2/5.7 mmHg, 11.1/8.0 mmHg with 
amlodipine 5 mg and 10 mg and higher diastolic blood pressure control rates compared to the respective 
monotherapies were achieved (56.7 %, 63.8 % with 40 mg/5 mg and 80 mg/5 mg versus 42-%, 56.7 %
with amlodipine 5 mg and 10 mg). Oedema rates were significantly lower with 40 mg/5 mg and 
80 mg/5 mg compared to amlodipine 10 mg (4.4 % versus 24.9 %, respectively).

In another multicentre, randomised, double-blind, active-controlled, parallel group study, a total of 
947 patients with mild to severe hypertension who were not adequately controlled on amlodipine 10 mg 
received Twynsta (40 mg/10 mg or 80 mg/10 mg) or amlodipine alone (10 mg). After 8 weeks of 
treatment, each of the combination treatments was statistically significantly superior to amlodipine 
monotherapy in reducing diastolic and systolic blood pressure (11.1/9.2 mmHg, 11.3/ 9.3 mmHg 
with 40 mg/10 mg, 80 mg/10 mg versus 7.4/6.5 mmHg with amlodipine 10 mg) and higher diastolic 
blood pressure normalisation rates compared to monotherapy were achieved (63.7 %, 66.5 % with 
40 mg/10 mg, 80 mg/10 mg versus 51.1 % with amlodipine 10 mg).

In two corresponding open-label long-term follow up studies performed over a further 6 months the 
effect of Twynsta was maintained over the trial period. Furthermore it was shown that some patients not 
adequately controlled with Twynsta 40 mg/10 mg had additional blood pressure reduction by up-titration 
to Twynsta 80 mg/10 mg.

The overall incidence of adverse reactions with Twynsta in the clinical trial programme was low with 
only 12.7 % of patients on treatment experiencing adverse reactions. The most common adverse reactions 
were peripheral oedema and dizziness, see also section 4.8. The adverse reactions reported were in 
agreement with those anticipated from the safety profiles of the components telmisartan and amlodipine. 
No new or more severe adverse reactions were observed. The oedema related events (peripheral oedema, 



36

generalised oedema, and oedema) were consistently lower in patients who received Twynsta as compared 
to patients who received amlodipine 10 mg. In the factorial design trial the oedema rates were 1.3 % with 
Twynsta 40 mg/5 mg and 80 mg/5 mg, 8.8 % with Twynsta 40 mg/10 mg and 80 mg/10 mg and 18.4 %
with Amlodipine 10 mg. In patients not controlled on amlodipine 5 mg the oedema rates were 4.4 % for 
40 mg/5 mg and 80 mg/5 mg and 24.9 % for amlodipine 10 mg.

The antihypertensive effect of Twynsta was similar irrespective of age and gender, and was similar in 
patients with and without diabetes.

Twynsta has not been studied in any patient population other than hypertension. Telmisartan has been 
studied in a large outcome study in 25,620 patients with high cardiovascular risk (ONTARGET). 
Amlodipine has been studied in patients with chronic stable angina, vasospastic angina and 
angiographically documented coronary artery disease.

Paediatric population
The European Medicines Agency has waived the obligation to submit the results of studies with Twynsta
in all subsets of the paediatric population in hypertension (see section 4.2 for information on paediatric 
use).

5.2 Pharmacokinetic properties

Pharmacokinetic of the fixed dose combination 
The rate and extent of absorption of Twynsta are equivalent to the bioavailability of telmisartan and 
amlodipine when administered as individual tablets.

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

After oral administration of therapeutic doses, amlodipine is well absorbed with peak blood levels 
between 6-12 hours post dose. Absolute bioavailability has been estimated to be between 64 and 80 %. 
Amlodipine bioavailability is not affected by food ingestion.

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

The volume of distribution of amlodipine is approximately 21 l/kg. In vitro studies have shown that 
approximately 97.5 % of circulating amlodipine is bound to plasma proteins in hypertensive patients.

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

Amlodipine is extensively (approximatively 90 %) metabolised by the liver to inactive metabolites.

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



37

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

Amlodipine elimination from plasma is biphasic, with a terminal elimination half-life of approximately 
30 to 50 hours consistent with once daily dosing. Steady-state plasma levels are reached after continuous 
administration for 7-8 days. Ten per cent of original amlodipine and 60 % of amlodipine metabolites are 
excreted in urine. 

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

Amlodipine exhibits linear pharmacokinetics. 

Paediatric population (age below 18 years)
No pharmacokinetic data are available in the paediatric population.

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

Elderly
The pharmacokinetics of telmisartan do not differ in young and elderly patients.
The time to reach peak plasma concentrations of amlodipine is similar in elderly and younger subjects. In 
elderly patients, amlodipine clearance tends to decline with resulting increases in AUC and elimination 
half-life.

Renal impairment
In patients with mild to moderate and severe renal impairment, doubling of plasma concentrations of 
telmisartan 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 
subjects and cannot be removed by dialysis. The elimination half-life is not changed in patients with 
renal impairment. The pharmacokinetics of amlodipine are not significantly influenced by renal 
impairment.

Hepatic impairment
Pharmacokinetic studies in patients with hepatic impairment showed an increase in absolute 
bioavailability of telmisartan up to nearly 100 %. The elimination half-life of telmisartan is not changed 
in patients with hepatic impairment. Patients with hepatic insufficiency have decreased clearance of 
amlodipine with resulting increase of approximately 40-60 % in AUC.

5.3 Preclinical safety data

Since the non-clinical toxicity profiles of telmisartan and amlodipine are not overlapping, no 
exacerbation of toxicity was expected for the combination. This has been confirmed in a subchronic 
(13-week) toxicology study in rats, in which dose levels of 3.2/0.8, 10/2.5 and 40/10 mg/kg of telmisartan 
and amlodipine were tested.

Preclinical data available for the components of this fixed dose combination are reported below.

Telmisartan
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 



38

normotensive animals. In dogs, renal tubular dilation and atrophy were observed. Gastric mucosal injury 
(erosion, ulcers or inflammation) also was noted in rats and dogs. These pharmacologically-mediated 
undesirable effects, known from preclinical studies with both angiotensin converting enzyme inhibitors 
and angiotensin II receptor antagonists, were prevented by oral saline supplementation. In both species, 
increased plasma renin activity and hypertrophy/hyperplasia of the renal juxtaglomerular cells were 
observed. These changes, also a class effect of angiotensin converting enzyme inhibitors and other 
angiotensin II receptor antagonists, do not appear to have clinical significance.
No clear evidence of a teratogenic effect was observed, however at toxic dose levels of telmisartan an 
effect on the postnatal development of the offspring such as lower body weight and delayed eye opening 
was observed.
There was no evidence of mutagenicity and relevant clastogenic activity in in vitro studies and no 
evidence of carcinogenicity in rats and mice.

Amlodipine

Reproductive toxicology
Reproductive studies in rats and mice have shown delayed date of delivery, prolonged duration of labour 
and decreased pup survival at dosages approximately 50 times greater than the maximum recommended 
dosage for humans based on mg/kg.

Impairment of fertility
There was no effect on the fertility of rats treated orally with amlodipine maleate (males for 64 days and 
females for 14 days prior to mating) at doses of up to 10 mg amlodipine/kg/day (about 8 times* the 
maximum recommended human dose of 10 mg/day on an mg/m2 basis). 
In another rat study in which male rats were treated with amlodipine besilate for 30 days at a dose 
comparable with the human dose based on mg/kg, decreased plasma follicle-stimulating hormone and 
testosterone were found as well as decreases in sperm density and in the number of mature spermatids 
and Sertoli cells.

Carcinogenesis, mutagenesis
Rats and mice treated with amlodipine in the diet for two years, at concentrations calculated to provide 
daily dosage levels of 0.5, 1.25, and 2.5 mg/kg/day showed no evidence of carcinogenicity. The highest 
dose (for mice, similar to, and for rats twice* the maximum recommended clinical dose of 10 mg on a 
mg/m2 basis) was close to the maximum tolerated dose for mice but not for rats.
Mutagenicity studies revealed no drug related effects at either the gene or chromosome levels.

*Based on patient weight of 50 kg

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Colloidal anhydrous silica
Brilliant blue FCF (E133)
Ferric oxide black (E172)
Ferric oxide yellow (E172)
Magnesium stearate
Maize starch
Meglumine
Microcrystalline cellulose
Povidone K25
Pregelatinised starch (prepared from maize starch)
Sodium hydroxide
Sorbitol (E420)



39

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years

6.4 Special precautions for storage

This medicinal product does not require any special temperature storage conditions.
Store in the original package in order to protect from light and moisture.
Remove the tablets from the blister only directly prior to intake.

6.5 Nature and contents of container

Aluminium/aluminium blisters (PA/Al/PVC/Al) in a carton containing 14, 28, 56, 98 tablets or 
aluminium/aluminium perforated unit dose blisters (PA/Al/PVC/Al) in a carton containing 30 x 1, 
90 x 1 tablets and multipacks containing 360 (4 packs of 90 x 1) tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

7. MARKETING AUTHORISATION HOLDER

Boehringer Ingelheim International GmbH
Binger Str. 173
D-55216 Ingelheim am Rhein
Germany

8. MARKETING AUTHORISATION NUMBERS

EU/1/10/648/008 (14 tablets)
EU/1/10/648/009 (28 tablets)
EU/1/10/648/010 (30 x 1 tablets)
EU/1/10/648/011 (56 tablets)
EU/1/10/648/012 (90 x 1 tablets)
EU/1/10/648/013 (98 tablets)
EU/1/10/648/014 (360 (4 x 90 x 1) tablets)

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 7 October 2010
Date of latest renewal: 20 August 2015

10. DATE OF REVISION OF THE TEXT

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

http://www.emea.europa.eu


40

1. NAME OF THE MEDICINAL PRODUCT

Twynsta 80 mg/5 mg tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 80 mg telmisartan and 5 mg amlodipine (as amlodipine besilate).

Excipient(s) with known effect: 
Each tablet contains 337.28 mg sorbitol (E420).
Each tablet contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Tablet

Blue and white oval shaped two layer tablets engraved with the product code A3 and the company logo 
on the white layer.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Treatment of essential hypertension in adults:

Add on therapy
Twynsta 80 mg/5 mg is indicated in adults whose blood pressure is not adequately controlled with 
Twynsta 40 mg/5 mg .

Replacement therapy
Adult patients receiving telmisartan and amlodipine from separate tablets can instead receive tablets of 
Twynsta containing the same component doses.

4.2 Posology and method of administration

Posology
The recommended dose of this medicinal product is one tablet per day.

The maximum recommended dose is one tablet 80 mg telmisartan/10 mg amlodipine per day. This 
medicinal product is indicated for long term treatment.

Administration of amlodipine with grapefruit or grapefruit juice is not recommended as bioavailability 
may be increased in some patients resulting in increased blood pressure lowering effects (see section 
4.5).

Add on therapy
Twynsta 80 mg/5 mg may be administered in patients whose blood pressure is not adequately controlled 
with Twynsta 40 mg/5 mg.



41

Individual dose titration with the components (i.e. amlodipine and telmisartan) is recommended before
changing to the fixed dose combination. When clinically appropriate, direct change from monotherapy to 
the fixed combination may be considered.

Patients treated with 10 mg amlodipine who experience any dose limiting adverse reactions such as 
oedema, may be switched to Twynsta 40 mg/5 mg once daily, reducing the dose of amlodipine without 
reducing the overall expected antihypertensive response.

Replacement therapy
Patients receiving telmisartan and amlodipine from separate tablets can instead receive tablets of 
Twynsta containing the same component doses in one tablet once daily. 

Elderly (> 65 years)
No dose adjustment is necessary for elderly patients. Little information is available in the very elderly 
patients.
Normal amlodipine dosage regimens are recommended in the elderly, but increase of dosage should take 
place with care (see section 4.4).

Renal impairment 
Limited experience is available in patients with severe renal impairment or haemodialysis. Caution is 
advised when using telmisartan/amlodipine in such patients as amlodipine and telmisartan are not 
dialysable (see also section 4.4).
No posology adjustment is required for patients with mild to moderate renal impairment.

Hepatic impairment
Twynsta is contraindicated in patients with severe hepatic impairment (see section 4.3).
In patients with mild to moderate hepatic impairment telmisartan/amlodipine should be administered with 
caution. For telmisartan the posology should not exceed 40 mg once daily (see section 4.4). 

Paediatric population
The safety and efficacy of telmisartan/amlodipine in children aged below 18 years have not been 
established. No data are available.

Method of administration
Oral use.
Twynsta can be taken with or without food. It is recommended to take Twynsta with some liquid.

4.3 Contraindications

 Hypersensitivity to the active substances, to dihydropyridine derivatives, or to any of the 
excipients listed in section 6.1

 Second and third trimesters of pregnancy (see sections 4.4 and 4.6)
 Biliary obstructive disorders and severe hepatic impairment
 Shock (including cardiogenic shock)
 Obstruction of the outflow tract of the left ventricle (e.g. high grade aortic stenosis) 
 Haemodynamically unstable heart failure after acute myocardial infarction

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



42

4.4 Special warnings and precautions for use

Pregnancy
Angiotensin II receptor antagonists should not be initiated during pregnancy. Unless continued 
angiotensin II receptor antagonist therapy is considered essential, patients planning pregnancy should be 
changed to alternative antihypertensive treatments which have an established safety profile for use in 
pregnancy. When pregnancy is diagnosed, treatment with angiotensin II receptor antagonists should be 
stopped immediately, and, if appropriate, alternative therapy should be started (see section 4.3 and 4.6).

Hepatic impairment
Telmisartan is mostly eliminated in the bile. Patients with biliary obstructive disorders or hepatic 
insufficiency can be expected to have reduced clearance. 
The half-life of amlodipine is prolonged and AUC values are higher in patients with impaired liver 
function; dosage recommendations have not been established. Amlodipine should therefore be initiated at 
the lower end of the dosing range and caution should be used, both on initial treatment and when 
increasing the dose. 
Telmisartan/amlodipine should therefore be used with caution in these patients.

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 (RAAS). 

Renal impairment and kidney transplantation
When telmisartan/amlodipine is used in patients with impaired renal function, a periodic monitoring of 
potassium and creatinine serum levels is recommended. There is no experience regarding the 
administration of telmisartan/amlodipine in patients with a recent kidney transplant. Telmisartan and 
amlodipine are not dialysable.

Intravascular hypovolaemia
Symptomatic hypotension, especially after the first dose, may occur in patients who are volume and/or 
sodium depleted by e.g. vigorous diuretic therapy, dietary salt restriction, diarrhoea or vomiting. Such 
conditions should be corrected before the administration of telmisartan. If hypotension occurs with 
telmisartan/amlodipine, the patient should be placed in the supine position and, if necessary, given an 
intravenous infusion of normal saline. Treatment can be continued once blood pressure has been 
stabilised.

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

Other conditions with stimulation of the renin-angiotensin-aldosterone system
In patients whose vascular tone and renal function depend predominantly on the activity of the 
renin-angiotensin-aldosterone system (e.g. patients with severe congestive heart failure or underlying 
renal disease, including renal artery stenosis), treatment with medicinal products that affect this system 
has been associated with acute hypotension, hyperazotaemia, oliguria, or rarely acute renal failure (see 
section 4.8).



43

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.

Unstable angina pectoris, acute myocardial infarction
There are no data to support the use of telmisartan/amlodipine in unstable angina pectoris and during or 
within one month of a myocardial infarction.

Patients with cardiac failure
In an amlodipine long-term, placebo controlled study in patients with severe heart failure (NYHA class 
III and IV) the reported incidence of pulmonary oedema was higher in the amlodipine treated group than 
in the placebo group (see section 5.1). Therefore, patients with heart failure should be treated with 
caution.
Calcium channel blockers, including amlodipine, should be used with caution in patients with congestive 
heart failure, as they may increase the risk of future cardiovascular events and mortality.

Diabetic patients treated with insulin or antidiabetics
In these patients hypoglycaemia may occur under telmisartan treatment. Therefore, in these patients an 
appropriate blood glucose monitoring should be considered; a dose adjustment of insulin or antidiabetics 
may be required when indicated.

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

Before considering the concomitant use of medicinal products that affect the 
renin-angiotensin-aldosterone system, the benefit risk ratio should be evaluated.
The main risk factors for hyperkalaemia to be considered are:
- Diabetes mellitus, renal impairment, age (>70 years)
- Combination with one or more other medicinal products that affect the 

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

- Intercurrent events, in particular dehydration, 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, extensive trauma).

Serum potassium should be monitored closely in these patients (see section 4.5).

Elderly patients
The increase of the amlodipine dosage should take place with care in the elderly patients (see section 4.2
and 5.2).

Sorbitol
This medicine contains 337.28 mg sorbitol in each tablet. 
Sorbitol is a source of fructose. Twynsta is not recommended for use in patients with hereditary fructose 
intolerance (HFI).



44

Other
As with any antihypertensive medicinal product, excessive reduction of blood pressure in patients with 
ischaemic cardiomyopathy or ischaemic cardiovascular disease could result in a myocardial infarction or 
stroke.

4.5 Interaction with other medicinal products and other forms of interaction

No interactions between the two components of this fixed dose combinations have been observed in 
clinical studies. 

Interactions linked to the combination
No drug interaction studies have been performed.

To be taken into account with concomitant use 

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

Medicinal products with blood pressure lowering potential
Based on their pharmacological properties it can be expected that the following medicinal products may 
potentiate the hypotensive effects of all antihypertensives including this medicinal product, e.g. baclofen, 
amifostine, neuroleptics or antidepressants. Furthermore, orthostatic hypotension may be aggravated by 
alcohol.

Corticosteroids (systemic route)
Reduction of the antihypertensive effect.

Interactions linked to telmisartan 

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. 

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



45

Concomitant use requiring caution

Non-steroidal anti-inflammatory medicinal products
NSAIDs (i.e. acetylsalicylic acid at anti-inflammatory dosage regimens, COX-2 inhibitors and non-
selective NSAIDs) may reduce the antihypertensive effect of angiotensin II receptor antagonists.
In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with 
compromised renal function), the co-administration of angiotensin II receptor antagonists and medicinal 
products 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.

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

Concomitant use to be taken into account

Digoxin
When telmisartan was co-administered with digoxin, median increases in digoxin peak plasma 
concentration (49 %) and in trough concentration (20 %) were observed. When initiating, adjusting, and 
discontinuing telmisartan, monitor digoxin levels in order to maintain levels within the therapeutic range.

Interactions linked to amlodipine

Concomitant use requiring caution

CYP3A4 inhibitors
Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors (protease inhibitors, azole 
antifungals, macrolides like erythromycin or clarithromycin, verapamil or diltiazem) may give rise to 
significant increase in amlodipine exposure resulting in an increased risk of hypotension. The clinical 
translation of these PK variations may be more pronounced in the elderly. Clinical monitoring and dose 
adjustment may thus be required.

CYP3A4 inducers
Upon co-administration of known inducers of the CYP3A4, the plasma concentration of amlodipine
may vary. Therefore, blood pressure should be monitored and dose regulation considered both
during and after concomitant medication particularly with strong CYP3A4 inducers (e.g.
rifampicin, hypericum perforatum).

Dantrolene (infusion)
In animals, lethal ventricular fibrillation and cardiovascular collapse are observed in association with 
hyperkalemia after administration of verapamil and intravenous dantrolene. Due to risk of hyperkalemia, 
it is recommended that the coadministration of calcium channel blockers such as amlodipine be avoided 
in patients susceptible to malignant hyperthermia and in the management of malignant hyperthermia.

Grapefruit and grapefruit juice
Administration of Twynsta with grapefruit or grapefruit juice is not recommended since bioavailability 
may be increased in certain patients resulting in increased blood pressure lowering effects.  



46

Concomitant use to be taken into account

Tacrolimus
There is a risk of increased tacrolimus blood levels when co-administered with amlodipine but the 
pharmacokinetic mechanism of this interaction is not fully understood. In order to avoid toxicity of 
tacrolimus, administration of amlodipine in a patient treated with tacrolimus requires monitoring of 
tacrolimus blood levels and dose adjustment of tacrolimus when appropriate.

Cyclosporine
No drug interaction studies have been conducted with cyclosporine and amlodipine in healthy volunteers 
or other populations with the exception of renal transplant patients, where variable trough concentration 
increases (average 0% - 40%) of cyclosporine were observed. Consideration should be given for 
monitoring cyclosporine levels in renal transplant patients on amlodipine, and cyclosporine dose 
reductions should be made as necessary.

Mechanistic Target of Rapamycin (mTOR) Inhibitors
mTOR inhibitors such as sirolimus, temsirolimus, and everolimus are CYP3A substrates. Amlodipine is a 
weak CYP3A inhibitor. With concomitant use of mTOR inhibitors, amlodipine may increase exposure of 
mTOR inhibitors.

Simvastatin
Co-administration of multiple doses of 10 mg of amlodipine with simvastatin 80 mg resulted in an 
increase in exposure to simvastatin up to 77 % compared to simvastatin alone. Therefore, the dose of 
simvastatin in patients on amlodipine should be limited to 20 mg daily.

4.6 Fertility, pregnancy and lactation

Pregnancy
There are limited data from the use of telmisartan/amlodipine in pregnant women. Animal reproductive 
toxicity studies with telmisartan/amlodipine have not been performed.

Telmisartan

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).

Studies with telmisartan 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 medicinal products. Unless continued angiotensin II 
receptor antagonist therapy is considered essential, patients planning pregnancy should be changed to 
alternative antihypertensive treatments which have an established safety profile for use in pregnancy. 
When pregnancy is diagnosed, treatment with angiotensin II receptor antagonists should be stopped 
immediately, and, if appropriate, alternative therapy should be started.

Exposure to angiotensin II receptor antagonist therapy during the second and third trimesters is known to 
induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and 
neonatal toxicity (renal failure, hypotension, hyperkalaemia) (see section 5.3).
Should exposure to angiotensin II receptor antagonists have occurred from the second trimester of 
pregnancy, ultrasound check of renal function and skull is recommended.
Infants whose mothers have taken angiotensin II receptor antagonists should be closely observed for 
hypotension (see sections 4.3 and 4.4).



47

Amlodipine

The safety of amlodipine in human pregnancy has not been established.
In animal studies, reproductive toxicity was observed at high doses (see section 5.3).

Breast-feeding
Amlodipine is excreted in human milk. The proportion of the maternal dose received by the infant has 
been estimated with an interquartile range of 3 – 7%, with a maximum of 15%. The effect of amlodipine 
on infants is unknown.
Because no information is available regarding the use of telmisartan during breast-feeding, 
telmisartan/amlodipine is not recommended and alternative treatments with better established safety 
profiles during breast-feeding are preferable, especially while breast-feeding a newborn or preterm 
infant.

Fertility
No data from controlled clinical studies with the fixed dose combination or with the individual 
components are available.

Separate reproductive toxicity studies with the combination of telmisartan and amlodipine have not been 
conducted.
In preclinical studies, no effects of telmisartan on male and female fertility were observed.
In some patients treated by calcium channel blockers, reversible biochemical changes in the head of 
spermatozoa have been reported. Clinical data are insufficient regarding the potential effect of 
amlodipine on fertility. In one rat study, adverse effects were found on male fertility (see section 5.3).

4.7 Effects on ability to drive and use machines

This medicinal product has moderate influence on the ability to drive and use machines. Patients should 
be advised that they may experience adverse reactions such as syncope, somnolence, dizziness, or vertigo 
during treatment (see section 4.8). Therefore, caution should be recommended when driving a car or 
using machines. If patients experience these adverse reactions, they should avoid potentially hazardous 
tasks such as driving or using machines.

4.8 Undesirable effects

Summary of the safety profile

The most common adverse reactions include dizziness and peripheral oedema. Serious syncope may 
occur rarely (less than 1 case per 1,000 patients).

Adverse reactions previously reported with one of the individual components (telmisartan or amlodipine) 
may be potential adverse reactions with Twynsta as well, even if not observed in clinical trials or during 
the post-marketing period.
Tabulated list of adverse reactions
The safety and tolerability of Twynsta has been evaluated in five controlled clinical studies with over 
3,500 patients, over 2,500 of whom received telmisartan in combination with amlodipine.

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.



48

System Organ
Class

Twynsta Telmisartan Amlodipine

Infections and infestations
Uncommon upper respiratory tract 

infection including 
pharyngitis and
sinusitis, urinary tract 
infection including 
cystitis

Rare cystitis sepsis including fatal 
outcome1

Blood and lymphatic system disorders:
Uncommon anaemia

Rare thrombocytopenia, 
eosinophilia 

Very rare leukocytopenia, 
thrombocytopenia

Immune system disorders:
Rare hypersensitivity, 

anaphylactic reaction

Very rare hypersensitivity

Metabolism and nutrition disorders
Uncommon hyperkalaemia

Rare hypoglycaemia (in 
diabetic patients)

Very rare hyperglycaemia

Psychiatric disorders
Uncommon mood change

Rare depression,
anxiety,
insomnia

confusion

Nervous system disorders
Common dizziness

Uncommon somnolence,
migraine,
headache,
paraesthesia

Rare syncope,
peripheral neuropathy,
hypoaesthesia,
dysgeusia,
tremor



49

Very rare extrapyramidal 
syndrome,
hypertonia

Eye disorders 
Common visual disturbance 

(including diplopia)
Uncommon visual impairment

Rare visual disturbance

Ear and labyrinth disorders
Uncommon vertigo tinnitus

Cardiac disorders
Uncommon bradycardia,

palpitations

Rare tachycardia

Very rare myocardial infarction, 
arrhythmia, 
ventricular tachycardia, 
atrial fibrillation

Vascular disorders
Uncommon hypotension,

orthostatic
hypotension, flushing

Very rare vasculitis

Respiratory, thoracic and mediastinal disorders
Uncommon cough dyspnoea dyspnoea, rhinitis

Very rare interstitial lung disease3

Gastrointestinal disorder
Common altered bowel habits 

(including diarrhoea 
and constipation)

Uncommon abdominal pain,
diarrhoea,
nausea

flatulence

Rare vomiting,
gingival hypertrophy,
dyspepsia,
dry mouth

stomach discomfort

Very rare pancreatitis, gastritis

Hepato-biliary disorders



50

Rare hepatic function 
abnormal, liver 
disorder2

Very rare hepatitis, jaundice, 
hepatic enzyme 
elevations (mostly 
consistent with 
cholestasis)

Skin and subcutaneous tissue disorders
Uncommon pruritus hyperhidrosis alopecia, purpura, skin 

discolouration, 
hyperhidrosis

Rare eczema, erythema,
rash

angioedema (with fatal 
outcome), 
drug eruption, 
toxic skin eruption, 
urticaria

Very rare angioedema, 
erythema multiforme, 
urticaria, 
exfoliative dermatitis, 
Stevens-Johnson 
syndrome, 
photosensitivity

Not known toxic epidermal 
necrolysis

Musculoskeletal and connective tissue disorders
Common ankle swelling

Uncommon arthralgia,
muscle spasms
(cramps in legs),
myalgia

Rare back pain,
pain in extremity (leg
pain)

tendon pain (tendinitis 
like symptoms)

Renal and urinary disorders
Uncommon renal impairment 

including acute renal 
failure

micturition disorder, 
pollakiuria

Rare nocturia

Reproductive system and breast disorders
Uncommon erectile dysfunction gynaecomastia

General disorders and administration site condition



51

Common peripheral oedema

Uncommon asthenia,
chest pain, fatigue,
oedema

pain

Rare malaise influenza-like illness

Investigations
Uncommon hepatic enzymes

increased
blood creatinine 
increased

weight increased, 
weight decreased

Rare blood uric acid
increased

blood creatine 
phosphokinase 
increased, haemoglobin 
decreased

1: the event may be a chance finding or related to a mechanism currently not known
2: most cases of hepatic function abnormal / liver disorder from post-marketing experience with 
telmisartan occurred in Japanese patients. Japanese patients are more likely to experience these adverse 
reactions.
3: cases of interstitial lung disease (predominantly interstitial pneumonia and eosinophilic pneumonia) 
have been reported from post-marketing experience with telmisartan

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

4.9 Overdose

Symptoms
Signs and symptoms of overdose are expected to be in line with exaggerated pharmacological effects. 
The most prominent manifestations of telmisartan overdose are expected to be hypotension and 
tachycardia; bradycardia, dizziness, increase in serum creatinine, and acute renal failure have also been 
reported.
Overdose with amlodipine may result in excessive peripheral vasodilatation and possibly reflex 
tachycardia. Marked and probably prolonged systemic hypotension up to and including shock with fatal 
outcome have been reported.

Treatment
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 
overdose of both telmisartan and amlodipine. 
Serum electrolytes and creatinine should be monitored frequently. If hypotension occurs, the patient 
should be placed in a supine position with elevation of extremities, with salt and volume replacement 
given quickly. Supportive treatment should be instituted. 
Intravenous calcium gluconate may be beneficial in reversing the effects of calcium channel blockade. 
Gastric lavage may be worthwhile in some cases. In healthy volunteers the use of charcoal up to 2 hours 
after administration of amlodipine 10 mg has been shown to reduce the absorption rate of amlodipine.
Telmisartan and Amlodipine are not removed by haemodialysis.

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


52

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Agents acting on the renin-angiotensin system, angiotensin II antagonists 
and calcium channel blockers; ATC Code: C09DB04.

Twynsta combines two antihypertensive compounds with complementary mechanisms to control blood 
pressure in patients with essential hypertension: an angiotensin II receptor antagonist, telmisartan, and a 
dihydropyridinic calcium channel blocker, amlodipine.
The combination of these substances has an additive antihypertensive effect, reducing blood pressure to a 
greater degree than either component alone.
Twynsta once daily produces effective and consistent reductions in blood pressure across the 24-hour 
therapeutic dose range.  

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

In humans, 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.

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. In this respect data concerning diastolic blood pressure 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 substances 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.

Two large randomised, controlled trials (ONTARGET (ONgoing Telmisartan Alone and in combination 
with Ramipril Global Endpoint Trial) and VA NEPHRON-D (The Veterans Affairs Nephropathy in 



53

Diabetes)) have examined the use of the combination of an ACE-inhibitor with an angiotensin II receptor 
blocker.
ONTARGET was a study conducted in patients with a history of cardiovascular or cerebrovascular 
disease, or type 2 diabetes mellitus accompanied by evidence of end-organ damage. VA NEPHRON-D 
was a study in patients with type 2 diabetes mellitus and diabetic nephropathy.
These studies have shown no significant beneficial effect on renal and/or cardiovascular outcomes and 
mortality, while an increased risk of hyperkalaemia, acute kidney injury and/or hypotension as compared 
to monotherapy was observed. Given their similar pharmacodynamic properties, these results are also 
relevant for other ACE-inhibitors and angiotensin II receptor blockers.
ACE-inhibitors and angiotensin II receptor blockers should therefore not be used concomitantly in 
patients with diabetic nephropathy.

ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) was 
a study designed to test the benefit of adding aliskiren to a standard therapy of an ACE-inhibitor or an 
angiotensin II receptor blocker in patients with type 2 diabetes mellitus and chronic kidney disease, 
cardiovascular disease, or both. The study was terminated early because of an increased risk of adverse 
outcomes. Cardiovascular death and stroke were both numerically more frequent in the aliskiren group 
than in the placebo group and adverse events and serious adverse events of interest (hyperkalaemia, 
hypotension and renal dysfunction) were more frequently reported in the aliskiren group than in the 
placebo group.

Amlodipine
Amlodipine is a calcium ion influx inhibitor of the dihydropyridine group (slow channel blocker or 
calcium ion antagonist) and inhibits the transmembrane influx of calcium ions into cardiac and vascular 
smooth muscle. The mechanism of the antihypertensive action of amlodipine is due to a direct relaxant 
effect on vascular smooth muscle, leading to reductions in peripheral vascular resistance and in blood 
pressure. Experimental data indicate that amlodipine binds to both dihydropyridine and non-
dihydropyridine binding sites. Amlodipine is relatively vessel-selective, with a greater effect on vascular 
smooth muscle cells than on cardiac muscle cells.

In patients with hypertension, once daily dosing provides clinically significant reductions of blood 
pressure in both the supine and standing positions throughout the 24 hour interval. Due to the slow onset 
of action, acute hypotension is not a feature of amlodipine administration.
In hypertensive patients with normal renal function, therapeutic doses of amlodipine resulted in a 
decrease in renal vascular resistance and an increase in glomerular filtration rate and effective renal 
plasma flow, without change in filtration fraction or proteinuria.

Amlodipine has not been associated with any adverse metabolic effects or changes in plasma lipids and is 
suitable for use in patients with asthma, diabetes, and gout.

Use in patients with heart failure
Haemodynamic studies and exercise based controlled clinical trials in NYHA Class II-IV heart failure 
patients have shown that amlodipine did not lead to clinical deterioration as measured by exercise 
tolerance, left ventricular ejection fraction and clinical symptomatology.

A placebo controlled study (PRAISE) designed to evaluate patients in NYHA Class III-IV heart failure 
receiving digoxin, diuretics and ACE inhibitors has shown that amlodipine did not lead to an increase in 
risk of mortality or combined mortality and morbidity with heart failure.

In a follow-up, long term, placebo controlled study (PRAISE-2) of amlodipine in patients with NYHA III 
and IV heart failure without clinical symptoms or objective findings suggestive of underlying ischaemic 
disease, on stable doses of ACE inhibitors, digitalis, and diuretics, amlodipine had no effect on total 
cardiovascular mortality. In this same population amlodipine was associated with increased reports of 
pulmonary oedema.



54

Telmisartan/Amlodipine
In an 8-week multicenter, randomised, double-blind, placebo-controlled, parallel group factorial study in 
1461 patients with mild to severe hypertension (mean seated diastolic blood pressure ≥95 and 
≤119 mmHg), treatment with each combination dose of Twynsta resulted in significantly greater diastolic 
and systolic blood pressure reductions and higher control rates compared to the respective monotherapy 
components.

Twynsta showed dose-related reductions in systolic/diastolic blood pressure across the therapeutic dose 
range of 21.8/16.5 mmHg (40 mg/5 mg), 22.1/18.2 mmHg (80 mg/5 mg), 24.7/20.2 mmHg 
(40 mg/10 mg) and 26.4/20.1 mmHg (80 mg/10 mg). The reduction in diastolic blood pressure 
<90 mmHg was achieved in 71.6 %, 74.8 %, 82.1 %, 85.3 % of patients respectively. Values are adjusted 
for baseline and country.

The majority of the antihypertensive effect was attained within 2 weeks after initiation of therapy.
In a subset of 1050 patients with moderate to severe hypertension (DBP ≥100 mmHg) 32.7-51.8 %
responded sufficiently to monotherapy of either telmisartan or amlodipine. The observed mean changes 
in systolic/diastolic blood pressure with a combination therapy containing amlodipine 5 mg 
(22.2/17.2 mmHg with 40 mg/5 mg; 22.5/19.1 mmHg with 80 mg/5 mg) were comparable to or 
greater than those seen with amlodipine 10 mg (21.0/17.6 mmHg) and associated with significant 
lower oedema rates (1.4 % with 40 mg/5 mg; 0.5 % with 80 mg/5 mg; 17.6 % with amlodipine 10 mg).

Automated ambulatory blood pressure monitoring (ABPM) performed in a subset of 562 patients 
confirmed the results seen with in-clinic systolic and diastolic blood pressure reductions consistently 
over the entire 24-hours dosing period.

In a further multicentre, randomised, double-blind, active-controlled, parallel group study, a total of 1097 
patients with mild to severe hypertension who were not adequately controlled on amlodipine 5 mg 
received Twynsta (40 mg/5 mg or 80 mg/5 mg) or amlodipine alone (5 mg or 10 mg). After 8 weeks of 
treatment, each of the combinations was statistically significantly superior to both amlodipine 
monotherapy doses in reducing systolic and diastolic blood pressures (13.6/9.4 mmHg, 
15.0/10.6 mmHg with 40 mg/5 mg, 80 mg/5 mg versus 6.2/5.7 mmHg, 11.1/8.0 mmHg with 
amlodipine 5 mg and 10 mg and higher diastolic blood pressure control rates compared to the respective 
monotherapies were achieved (56.7 %, 63.8 % with 40 mg/5 mg and 80 mg/5 mg versus 42 %, 56.7 %
with amlodipine 5 mg and 10 mg). Oedema rates were significantly lower with 40 mg/5 mg and 
80 mg/5 mg compared to amlodipine 10 mg (4.4 % versus 24.9 %, respectively).

In another multicentre, randomised, double-blind, active-controlled, parallel group study, a total of 
947 patients with mild to severe hypertension who were not adequately controlled on amlodipine 10 mg 
received Twynsta (40 mg/10 mg or 80 mg/10 mg) or amlodipine alone (10 mg). After 8 weeks of 
treatment, each of the combination treatments was statistically significantly superior to amlodipine 
monotherapy in reducing diastolic and systolic blood pressure (11.1/9.2 mmHg, 11.3/ 9.3 mmHg 
with 40 mg/10 mg, 80 mg/10 mg versus 7.4/6.5 mmHg with amlodipine 10 mg) and higher diastolic 
blood pressure normalisation rates compared to monotherapy were achieved (63.7 %, 66.5 % with 
40 mg/10 mg, 80 mg/10 mg versus 51.1 % with amlodipine 10 mg).

In two corresponding open-label long-term follow up studies performed over a further 6 months the 
effect of Twynsta was maintained over the trial period. Furthermore it was shown that some patients not 
adequately controlled with Twynsta 40 mg/10 mg had additional blood pressure reduction by up-titration 
to Twynsta 80 mg/10 mg.

The overall incidence of adverse reactions with Twynsta in the clinical trial programme was low with 
only 12.7 % of patients on treatment experiencing adverse reactions. The most common adverse reactions 
were peripheral oedema and dizziness, see also section 4.8. The adverse reactions reported were in 
agreement with those anticipated from the safety profiles of the components telmisartan and amlodipine. 
No new or more severe adverse reactions were observed. The oedema related events (peripheral oedema, 



55

generalised oedema, and oedema) were consistently lower in patients who received Twynsta as compared 
to patients who received amlodipine 10 mg. In the factorial design trial the oedema rates were 1.3 % with 
Twynsta 40 mg/5 mg and 80 mg/5 mg, 8.8 % with Twynsta 40 mg/10 mg and 80 mg/10 mg and 18.4 %
with Amlodipine 10 mg. In patients not controlled on amlodipine 5 mg the oedema rates were 4.4 % for 
40 mg/5 mg and 80 mg/5 mg and 24.9 % for amlodipine 10 mg.

The antihypertensive effect of Twynsta was similar irrespective of age and gender, and was similar in 
patients with and without diabetes.

Twynsta has not been studied in any patient population other than hypertension. Telmisartan has been 
studied in a large outcome study in 25,620 patients with high cardiovascular risk (ONTARGET). 
Amlodipine has been studied in patients with chronic stable angina, vasospastic angina and 
angiographically documented coronary artery disease.

Paediatric population
The European Medicines Agency has waived the obligation to submit the results of studies with Twynsta
in all subsets of the paediatric population in hypertension (see section 4.2 for information on paediatric 
use).

5.2 Pharmacokinetic properties

Pharmacokinetic of the fixed dose combination 
The rate and extent of absorption of Twynsta are equivalent to the bioavailability of telmisartan and 
amlodipine when administered as individual tablets.

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

After oral administration of therapeutic doses, amlodipine is well absorbed with peak blood levels 
between 6-12 hours post dose. Absolute bioavailability has been estimated to be between 64 and 80 %. 
Amlodipine bioavailability is not affected by food ingestion.

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

The volume of distribution of amlodipine is approximately 21 l/kg. In vitro studies have shown that 
approximately 97.5 % of circulating amlodipine is bound to plasma proteins in hypertensive patients.

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

Amlodipine is extensively (approximatively 90 %) metabolised by the liver to inactive metabolites.

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



56

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

Amlodipine elimination from plasma is biphasic, with a terminal elimination half-life of approximately 
30 to 50 hours consistent with once daily dosing. Steady-state plasma levels are reached after continuous 
administration for 7-8 days. Ten per cent of original amlodipine and 60 % of amlodipine metabolites are 
excreted in urine. 

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

Amlodipine exhibits linear pharmacokinetics. 

Paediatric population (age below 18 years)
No pharmacokinetic data are available in the paediatric population.

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

Elderly
The pharmacokinetics of telmisartan do not differ in young and elderly patients.
The time to reach peak plasma concentrations of amlodipine is similar in elderly and younger subjects. In 
elderly patients, amlodipine clearance tends to decline with resulting increases in AUC and elimination 
half-life.

Renal impairment
In patients with mild to moderate and severe renal impairment, doubling of plasma concentrations of 
telmisartan 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 
subjects and cannot be removed by dialysis. The elimination half-life is not changed in patients with 
renal impairment. The pharmacokinetics of amlodipine are not significantly influenced by renal 
impairment.

Hepatic impairment
Pharmacokinetic studies in patients with hepatic impairment showed an increase in absolute 
bioavailability of telmisartan up to nearly 100 %. The elimination half-life of telmisartan is not changed 
in patients with hepatic impairment. Patients with hepatic insufficiency have decreased clearance of 
amlodipine with resulting increase of approximately 40-60 % in AUC.

5.3 Preclinical safety data

Since the non-clinical toxicity profiles of telmisartan and amlodipine are not overlapping, no 
exacerbation of toxicity was expected for the combination. This has been confirmed in a subchronic 
(13-week) toxicology study in rats, in which dose levels of 3.2/0.8, 10/2.5 and 40/10 mg/kg of telmisartan 
and amlodipine were tested.

Preclinical data available for the components of this fixed dose combination are reported below.

Telmisartan
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 



57

normotensive animals. In dogs, renal tubular dilation and atrophy were observed. Gastric mucosal injury 
(erosion, ulcers or inflammation) also was noted in rats and dogs. These pharmacologically-mediated 
undesirable effects, known from preclinical studies with both angiotensin converting enzyme inhibitors 
and angiotensin II receptor antagonists, were prevented by oral saline supplementation. In both species, 
increased plasma renin activity and hypertrophy/hyperplasia of the renal juxtaglomerular cells were 
observed. These changes, also a class effect of angiotensin converting enzyme inhibitors and other 
angiotensin II receptor antagonists, do not appear to have clinical significance.
No clear evidence of a teratogenic effect was observed, however at toxic dose levels of telmisartan an 
effect on the postnatal development of the offspring such as lower body weight and delayed eye opening 
was observed.
There was no evidence of mutagenicity and relevant clastogenic activity in in vitro studies and no 
evidence of carcinogenicity in rats and mice.

Amlodipine

Reproductive toxicology
Reproductive studies in rats and mice have shown delayed date of delivery, prolonged duration of labour 
and decreased pup survival at dosages approximately 50 times greater than the maximum recommended 
dosage for humans based on mg/kg.

Impairment of fertility
There was no effect on the fertility of rats treated orally with amlodipine maleate (males for 64 days and 
females for 14 days prior to mating) at doses of up to 10 mg amlodipine/kg/day (about 8 times* the 
maximum recommended human dose of 10 mg/day on an mg/m2 basis). 
In another rat study in which male rats were treated with amlodipine besilate for 30 days at a dose 
comparable with the human dose based on mg/kg, decreased plasma follicle-stimulating hormone and 
testosterone were found as well as decreases in sperm density and in the number of mature spermatids 
and Sertoli cells.

Carcinogenesis, mutagenesis
Rats and mice treated with amlodipine in the diet for two years, at concentrations calculated to provide 
daily dosage levels of 0.5, 1.25, and 2.5 mg/kg/day showed no evidence of carcinogenicity. The highest 
dose (for mice, similar to, and for rats twice* the maximum recommended clinical dose of 10 mg on a 
mg/m2 basis) was close to the maximum tolerated dose for mice but not for rats.
Mutagenicity studies revealed no drug related effects at either the gene or chromosome levels.

*Based on patient weight of 50 kg

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Colloidal anhydrous silica
Brilliant blue FCF (E133)
Ferric oxide black (E172)
Ferric oxide yellow (E172)
Magnesium stearate
Maize starch
Meglumine
Microcrystalline cellulose
Povidone K25
Pregelatinised starch (prepared from maize starch)
Sodium hydroxide
Sorbitol (E420)



58

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years

6.4 Special precautions for storage

This medicinal product does not require any special temperature storage conditions.
Store in the original package in order to protect from light and moisture.
Remove the tablets from the blister only directly prior to intake.

6.5 Nature and contents of container

Aluminium/aluminium blisters (PA/Al/PVC/Al) in a carton containing 14, 28, 56, 98 tablets or 
aluminium/aluminium perforated unit dose blisters (PA/Al/PVC/Al) in a carton containing 30 x 1, 
90 x 1 tablets and multipacks containing 360 (4 packs of 90 x 1) tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

7. MARKETING AUTHORISATION HOLDER

Boehringer Ingelheim International GmbH
Binger Str. 173
D-55216 Ingelheim am Rhein
Germany

8. MARKETING AUTHORISATION NUMBERS

EU/1/10/648/015 (14 tablets)
EU/1/10/648/016 (28 tablets)
EU/1/10/648/017 (30 x 1 tablets)
EU/1/10/648/018 (56 tablets)
EU/1/10/648/019 (90 x 1 tablets)
EU/1/10/648/020 (98 tablets)
EU/1/10/648/021 (360 (4 x 90 x 1) tablets)

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 7 October 2010
Date of latest renewal: 20 August 2015

10. DATE OF REVISION OF THE TEXT

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

http://www.emea.europa.eu


59

1. NAME OF THE MEDICINAL PRODUCT

Twynsta 80 mg/10 mg tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 80 mg telmisartan and 10 mg amlodipine (as amlodipine besilate).

Excipient(s) with known effect: 
Each tablet contains 337.28 mg sorbitol (E420).
Each tablet contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Tablet

Blue and white oval shaped two layer tablets engraved with the product code A4 and the company logo 
on the white layer.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Treatment of essential hypertension in adults:

Add on therapy
Twynsta 80 mg/10 mg is indicated in adults whose blood pressure is not adequately controlled on on 
Twynsta 40 mg/10 mg or Twynsta 80 mg/5 mg.

Replacement therapy
Adult patients receiving telmisartan and amlodipine from separate tablets can instead receive tablets of 
Twynsta containing the same component doses.

4.2 Posology and method of administration

Posology
The recommended dose of this medicinal product is one tablet per day.

The maximum recommended dose is one tablet 80 mg telmisartan/10 mg amlodipine per day. This 
medicinal product is indicated for long term treatment.

Administration of amlodipine with grapefruit or grapefruit juice is not recommended as bioavailability 
may be increased in some patients resulting in increased blood pressure lowering effects (see section 
4.5).

Add on therapy
Twynsta 80 mg/10 mg may be administered in patients whose blood pressure is not adequately controlled 
on Twynsta 40 mg/10 mg or Twynsta 80 mg/5 mg.



60

Individual dose titration with the components (i.e. amlodipine and telmisartan) is recommended before
changing to the fixed dose combination. When clinically appropriate, direct change from monotherapy to 
the fixed combination may be considered.

Patients treated with 10 mg amlodipine who experience any dose limiting adverse reactions such as 
oedema, may be switched to Twynsta 40 mg/5 mg once daily, reducing the dose of amlodipine without 
reducing the overall expected antihypertensive response.

Replacement therapy
Patients receiving telmisartan and amlodipine from separate tablets can instead receive tablets of 
Twynsta containing the same component doses in one tablet once daily. .

Elderly (> 65 years)
No dose adjustment is necessary for elderly patients. Little information is available in the very elderly 
patients.
Normal amlodipine dosage regimens are recommended in the elderly, but increase of dosage should take 
place with care (see section 4.4).

Renal impairment 
Limited experience is available in patients with severe renal impairment or haemodialysis. Caution is 
advised when using telmisartan/amlodipine in such patients as amlodipine and telmisartan are not 
dialysable (see also section 4.4).
No posology adjustment is required for patients with mild to moderate renal impairment.

Hepatic impairment
Twynsta is contraindicated in patients with severe hepatic impairment (see section 4.3).
In patients with mild to moderate hepatic impairment telmisartan/amlodipine should be administered with 
caution. For telmisartan the posology should not exceed 40 mg once daily (see section 4.4). 

Paediatric population
The safety and efficacy of telmisartan/amlodipine in children aged below 18 years have not been 
established. No data are available.

Method of administration
Oral use.
Twynsta can be taken with or without food. It is recommended to take Twynsta with some liquid.

4.3 Contraindications

 Hypersensitivity to the active substances, to dihydropyridine derivatives, or to any of the 
excipients listed in section 6.1

 Second and third trimesters of pregnancy (see sections 4.4 and 4.6)
 Biliary obstructive disorders and severe hepatic impairment
 Shock (including cardiogenic shock)
 Obstruction of the outflow tract of the left ventricle (e.g. high grade aortic stenosis) 
 Haemodynamically unstable heart failure after acute myocardial infarction

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



61

4.4 Special warnings and precautions for use

Pregnancy
Angiotensin II receptor antagonists should not be initiated during pregnancy. Unless continued 
angiotensin II receptor antagonist therapy is considered essential, patients planning pregnancy should be 
changed to alternative antihypertensive treatments which have an established safety profile for use in 
pregnancy. When pregnancy is diagnosed, treatment with angiotensin II receptor antagonists should be 
stopped immediately, and, if appropriate, alternative therapy should be started (see section 4.3 and 4.6).

Hepatic impairment
Telmisartan is mostly eliminated in the bile. Patients with biliary obstructive disorders or hepatic 
insufficiency can be expected to have reduced clearance.
The half-life of amlodipine is prolonged and AUC values are higher in patients with impaired liver 
function; dosage recommendations have not been established. Amlodipine should therefore be initiated at 
the lower end of the dosing range and caution should be used, both on initial treatment and when 
increasing the dose.
Telmisartan/amlodipine should therefore be used with caution in these patients.

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 (RAAS). 

Renal impairment and kidney transplantation
When telmisartan/amlodipine is used in patients with impaired renal function, a periodic monitoring of 
potassium and creatinine serum levels is recommended. There is no experience regarding the 
administration of telmisartan/amlodipine in patients with a recent kidney transplant. Telmisartan and 
amlodipine are not dialysable.

Intravascular hypovolaemia
Symptomatic hypotension, especially after the first dose, may occur in patients who are volume and/or 
sodium depleted by e.g. vigorous diuretic therapy, dietary salt restriction, diarrhoea or vomiting. Such 
conditions should be corrected before the administration of telmisartan. If hypotension occurs with 
telmisartan/amlodipine, the patient should be placed in the supine position and, if necessary, given an 
intravenous infusion of normal saline. Treatment can be continued once blood pressure has been 
stabilised.

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

Other conditions with stimulation of the renin-angiotensin-aldosterone system
In patients whose vascular tone and renal function depend predominantly on the activity of the 
renin-angiotensin-aldosterone system (e.g. patients with severe congestive heart failure or underlying 
renal disease, including renal artery stenosis), treatment with medicinal products that affect this system 
has been associated with acute hypotension, hyperazotaemia, oliguria, or rarely acute renal failure (see 
section 4.8).



62

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.

Unstable angina pectoris, acute myocardial infarction
There are no data to support the use of telmisartan/amlodipine in unstable angina pectoris and during or 
within one month of a myocardial infarction.

Patients with cardiac failure
In an amlodipine long-term, placebo controlled study in patients with severe heart failure (NYHA class 
III and IV) the reported incidence of pulmonary oedema was higher in the amlodipine treated group than 
in the placebo group (see section 5.1). Therefore, patients with heart failure should be treated with 
caution.
Calcium channel blockers, including amlodipine, should be used with caution in patients with congestive 
heart failure, as they may increase the risk of future cardiovascular events and mortality.

Diabetic patients treated with insulin or antidiabetics
In these patients hypoglycaemia may occur under telmisartan treatment. Therefore, in these patients an 
appropriate blood glucose monitoring should be considered; a dose adjustment of insulin or antidiabetics 
may be required when indicated.

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

Before considering the concomitant use of medicinal products that affect the 
renin-angiotensin-aldosterone system, the benefit risk ratio should be evaluated.
The main risk factors for hyperkalaemia to be considered are:
- Diabetes mellitus, renal impairment, age (>70 years)
- Combination with one or more other medicinal products that affect the 

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

- Intercurrent events, in particular dehydration, 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, extensive trauma).

Serum potassium should be monitored closely in these patients (see section 4.5).

Elderly patients
The increase of the amlodipine dosage should take place with care in the elderly patients (see section 4.2
and 5.2).

Sorbitol
This medicine contains 337.28 mg sorbitol in each tablet. 
Sorbitol is a source of fructose. Twynsta is not recommended for use in patients with hereditary fructose 
intolerance (HFI).



63

Other
As with any antihypertensive medicinal product, excessive reduction of blood pressure in patients with 
ischaemic cardiomyopathy or ischaemic cardiovascular disease could result in a myocardial infarction or 
stroke.

4.5 Interaction with other medicinal products and other forms of interaction

No interactions between the two components of this fixed dose combinations have been observed in 
clinical studies. 

Interactions linked to the combination
No drug interaction studies have been performed.

To be taken into account with concomitant use 

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

Medicinal products with blood pressure lowering potential
Based on their pharmacological properties it can be expected that the following medicinal products may 
potentiate the hypotensive effects of all antihypertensives including this medicinal product, e.g. baclofen, 
amifostine, neuroleptics or antidepressants. Furthermore, orthostatic hypotension may be aggravated by 
alcohol.

Corticosteroids (systemic route)
Reduction of the antihypertensive effect.

Interactions linked to telmisartan 

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. 

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



64

Concomitant use requiring caution

Non-steroidal anti-inflammatory medicinal products
NSAIDs (i.e. acetylsalicylic acid at anti-inflammatory dosage regimens, COX-2 inhibitors and non-
selective NSAIDs) may reduce the antihypertensive effect of angiotensin II receptor antagonists.
In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with
compromised renal function), the co-administration of angiotensin II receptor antagonists and medicinal 
products 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.

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

Concomitant use to be taken into account

Digoxin
When telmisartan was co-administered with digoxin, median increases in digoxin peak plasma 
concentration (49 %) and in trough concentration (20 %) were observed. When initiating, adjusting, and 
discontinuing telmisartan, monitor digoxin levels in order to maintain levels within the therapeutic range.

Interactions linked to amlodipine

Concomitant use requiring caution

CYP3A4 inhibitors
Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors (protease inhibitors, azole 
antifungals, macrolides like erythromycin or clarithromycin, verapamil or diltiazem) may give rise to 
significant increase in amlodipine exposure resulting in an increased risk of hypotension. The clinical 
translation of these PK variations may be more pronounced in the elderly. Clinical monitoring and dose 
adjustment may thus be required.

CYP3A4 inducers
Upon co-administration of known inducers of the CYP3A4, the plasma concentration of amlodipine
may vary. Therefore, blood pressure should be monitored and dose regulation considered both
during and after concomitant medication particularly with strong CYP3A4 inducers (e.g.
rifampicin, hypericum perforatum).

Dantrolene (infusion)
In animals, lethal ventricular fibrillation and cardiovascular collapse are observed in association with 
hyperkalemia after administration of verapamil and intravenous dantrolene. Due to risk of hyperkalemia, 
it is recommended that the coadministration of calcium channel blockers such as amlodipine be avoided 
in patients susceptible to malignant hyperthermia and in the management of malignant hyperthermia.

Grapefruit and grapefruit juice
Administration of Twynsta with grapefruit or grapefruit juice is not recommended since bioavailability 
may be increased in certain patients resulting in increased blood pressure lowering effects.  



65

Concomitant use to be taken into account

Tacrolimus
There is a risk of increased tacrolimus blood levels when co-administered with amlodipine but the 
pharmacokinetic mechanism of this interaction is not fully understood. In order to avoid toxicity of 
tacrolimus, administration of amlodipine in a patient treated with tacrolimus requires monitoring of 
tacrolimus blood levels and dose adjustment of tacrolimus when appropriate.

Cyclosporine
No drug interaction studies have been conducted with cyclosporine and amlodipine in healthy volunteers 
or other populations with the exception of renal transplant patients, where variable trough concentration 
increases (average 0% - 40%) of cyclosporine were observed. Consideration should be given for 
monitoring cyclosporine levels in renal transplant patients on amlodipine, and cyclosporine dose 
reductions should be made as necessary.

Mechanistic Target of Rapamycin (mTOR) Inhibitors
mTOR inhibitors such as sirolimus, temsirolimus, and everolimus are CYP3A substrates. Amlodipine is a 
weak CYP3A inhibitor. With concomitant use of mTOR inhibitors, amlodipine may increase exposure of 
mTOR inhibitors.

Simvastatin
Co-administration of multiple doses of 10 mg of amlodipine with simvastatin 80 mg resulted in an 
increase in exposure to simvastatin up to 77 % compared to simvastatin alone. Therefore, the dose of 
simvastatin in patients on amlodipine should be limited to 20 mg daily.

4.6 Fertility, pregnancy and lactation

Pregnancy
There are limited data from the use of telmisartan/amlodipine in pregnant women. Animal reproductive 
toxicity studies with telmisartan/amlodipine have not been performed.

Telmisartan

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).

Studies with telmisartan 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 medicinal products. Unless continued angiotensin II 
receptor antagonist therapy is considered essential, patients planning pregnancy should be changed to 
alternative antihypertensive treatments which have an established safety profile for use in pregnancy. 
When pregnancy is diagnosed, treatment with angiotensin II receptor antagonists should be stopped 
immediately, and, if appropriate, alternative therapy should be started.

Exposure to angiotensin II receptor antagonist therapy during the second and third trimesters is known to 
induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and 
neonatal toxicity (renal failure, hypotension, hyperkalaemia) (see section 5.3).
Should exposure to angiotensin II receptor antagonists have occurred from the second trimester of 
pregnancy, ultrasound check of renal function and skull is recommended.
Infants whose mothers have taken angiotensin II receptor antagonists should be closely observed for 
hypotension (see sections 4.3 and 4.4).



66

Amlodipine

The safety of amlodipine in human pregnancy has not been established.
In animal studies, reproductive toxicity was observed at high doses (see section 5.3).

Breast-feeding
Amlodipine is excreted in human milk. The proportion of the maternal dose received by the infant has 
been estimated with an interquartile range of 3 – 7%, with a maximum of 15%. The effect of amlodipine 
on infants is unknown.
Because no information is available regarding the use of telmisartan during breast-feeding, 
telmisartan/amlodipine is not recommended and alternative treatments with better established safety 
profiles during breast-feeding are preferable, especially while breast-feeding a newborn or preterm 
infant.

Fertility
No data from controlled clinical studies with the fixed dose combination or with the individual 
components are available.

Separate reproductive toxicity studies with the combination of telmisartan and amlodipine have not been 
conducted.
In preclinical studies, no effects of telmisartan on male and female fertility were observed.
In some patients treated by calcium channel blockers, reversible biochemical changes in the head of 
spermatozoa have been reported. Clinical data are insufficient regarding the potential effect of 
amlodipine on fertility. In one rat study, adverse effects were found on male fertility (see section 5.3).

4.7 Effects on ability to drive and use machines

This medicinal product has moderate influence on the ability to drive and use machines. Patients should 
be advised that they may experience adverse reactions such as syncope, somnolence, dizziness, or vertigo 
during treatment (see section 4.8). Therefore, caution should be recommended when driving a car or 
using machines. If patients experience these adverse reactions, they should avoid potentially hazardous 
tasks such as driving or using machines.

4.8 Undesirable effects

Summary of the safety profile

The most common adverse reactions include dizziness and peripheral oedema. Serious syncope may 
occur rarely (less than 1 case per 1,000 patients).

Adverse reactions previously reported with one of the individual components (telmisartan or amlodipine) 
may be potential adverse reactions with Twynsta as well, even if not observed in clinical trials or during 
the post-marketing period.

Tabulated list of adverse reactions
The safety and tolerability of Twynsta has been evaluated in five controlled clinical studies with over 
3,500 patients, over 2,500 of whom received telmisartan in combination with amlodipine.

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.



67

System Organ
Class

Twynsta Telmisartan Amlodipine

Infections and infestations
Uncommon upper respiratory tract 

infection including 
pharyngitis and
sinusitis, urinary tract 
infection including 
cystitis

Rare cystitis sepsis including fatal 
outcome1

Blood and lymphatic system disorders:
Uncommon anaemia

Rare thrombocytopenia, 
eosinophilia 

Very rare leukocytopenia, 
thrombocytopenia

Immune system disorders:
Rare hypersensitivity, 

anaphylactic reaction

Very rare hypersensitivity

Metabolism and nutrition disorders
Uncommon hyperkalaemia

Rare hypoglycaemia (in 
diabetic patients)

Very rare hyperglycaemia

Psychiatric disorders
Uncommon mood change

Rare depression,
anxiety,
insomnia

confusion

Nervous system disorders
Common dizziness

Uncommon somnolence,
migraine,
headache,
paraesthesia

Rare syncope,
peripheral neuropathy,
hypoaesthesia,
dysgeusia,
tremor



68

Very rare extrapyramidal 
syndrome,
hypertonia

Eye disorders 
Common visual disturbance 

(including diplopia)
Uncommon visual impairment

Rare visual disturbance

Ear and labyrinth disorders
Uncommon vertigo tinnitus

Cardiac disorders
Uncommon bradycardia,

palpitations

Rare tachycardia

Very rare myocardial infarction, 
arrhythmia, 
ventricular tachycardia, 
atrial fibrillation

Vascular disorders
Uncommon hypotension,

orthostatic
hypotension, flushing

Very rare vasculitis

Respiratory, thoracic and mediastinal disorders
Uncommon cough dyspnoea dyspnoea, rhinitis

Very rare interstitial lung disease3

Gastrointestinal disorder
Common altered bowel habits 

(including diarrhoea 
and constipation)

Uncommon abdominal pain,
diarrhoea,
nausea

flatulence

Rare vomiting,
gingival hypertrophy,
dyspepsia,
dry mouth

stomach discomfort

Very rare pancreatitis, gastritis

Hepato-biliary disorders



69

Rare hepatic function 
abnormal, liver 
disorder2

Very rare hepatitis, jaundice, 
hepatic enzyme 
elevations (mostly 
consistent with 
cholestasis)

Skin and subcutaneous tissue disorders
Uncommon pruritus hyperhidrosis alopecia, purpura, skin 

discolouration, 
hyperhidrosis

Rare eczema, erythema,
rash

angioedema (with fatal 
outcome), 
drug eruption, 
toxic skin eruption, 
urticaria

Very rare angioedema, 
erythema multiforme, 
urticaria, 
exfoliative dermatitis, 
Stevens-Johnson 
syndrome, 
photosensitivity

Not known toxic epidermal 
necrolysis

Musculoskeletal and connective tissue disorders
Common ankle swelling

Uncommon arthralgia,
muscle spasms
(cramps in legs),
myalgia

Rare back pain,
pain in extremity (leg
pain)

tendon pain (tendinitis 
like symptoms)

Renal and urinary disorders
Uncommon renal impairment 

including acute renal 
failure

micturition disorder, 
pollakiuria

Rare nocturia

Reproductive system and breast disorders
Uncommon erectile dysfunction gynaecomastia

General disorders and administration site condition



70

Common peripheral oedema

Uncommon asthenia,
chest pain, fatigue,
oedema

pain

Rare malaise influenza-like illness
Investigations
Uncommon hepatic enzymes

increased
blood creatinine 
increased

weight increased, 
weight decreased

Rare blood uric acid
increased

blood creatine 
phosphokinase 
increased, haemoglobin 
decreased

1: the event may be a chance finding or related to a mechanism currently not known
2: most cases of hepatic function abnormal / liver disorder from post-marketing experience with 
telmisartan occurred in Japanese patients. Japanese patients are more likely to experience these adverse 
reactions.
3: cases of interstitial lung disease (predominantly interstitial pneumonia and eosinophilic pneumonia) 
have been reported from post-marketing experience with telmisartan

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

4.9 Overdose

Symptoms
Signs and symptoms of overdose are expected to be in line with exaggerated pharmacological effects. 
The most prominent manifestations of telmisartan overdose are expected to be hypotension and 
tachycardia; bradycardia, dizziness, increase in serum creatinine, and acute renal failure have also been 
reported.
Overdose with amlodipine may result in excessive peripheral vasodilatation and possibly reflex 
tachycardia. Marked and probably prolonged systemic hypotension up to and including shock with fatal 
outcome have been reported.

Treatment
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
overdose of both telmisartan and amlodipine. 
Serum electrolytes and creatinine should be monitored frequently. If hypotension occurs, the patient 
should be placed in a supine position with elevation of extremities, with salt and volume replacement 
given quickly. Supportive treatment should be instituted. 
Intravenous calcium gluconate may be beneficial in reversing the effects of calcium channel blockade. 
Gastric lavage may be worthwhile in some cases. In healthy volunteers the use of charcoal up to 2 hours 
after administration of amlodipine 10 mg has been shown to reduce the absorption rate of amlodipine.
Telmisartan and Amlodipine are not removed by haemodialysis.

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


71

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Agents acting on the renin-angiotensin system, angiotensin II antagonists 
and calcium channel blockers; ATC Code: C09DB04.

Twynsta combines two antihypertensive compounds with complementary mechanisms to control blood 
pressure in patients with essential hypertension: an angiotensin II receptor antagonist, telmisartan, and a 
dihydropyridinic calcium channel blocker, amlodipine.
The combination of these substances has an additive antihypertensive effect, reducing blood pressure to a 
greater degree than either component alone.
Twynsta once daily produces effective and consistent reductions in blood pressure across the 24-hour 
therapeutic dose range.  

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

In humans, 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.

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. In this respect data concerning diastolic blood pressure 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 substances 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.

Two large randomised, controlled trials (ONTARGET (ONgoing Telmisartan Alone and in combination 
with Ramipril Global Endpoint Trial) and VA NEPHRON-D (The Veterans Affairs Nephropathy in 



72

Diabetes)) have examined the use of the combination of an ACE-inhibitor with an angiotensin II receptor 
blocker.
ONTARGET was a study conducted in patients with a history of cardiovascular or cerebrovascular 
disease, or type 2 diabetes mellitus accompanied by evidence of end-organ damage. VA NEPHRON-D 
was a study in patients with type 2 diabetes mellitus and diabetic nephropathy.
These studies have shown no significant beneficial effect on renal and/or cardiovascular outcomes and 
mortality, while an increased risk of hyperkalaemia, acute kidney injury and/or hypotension as compared 
to monotherapy was observed. Given their similar pharmacodynamic properties, these results are also 
relevant for other ACE-inhibitors and angiotensin II receptor blockers.
ACE-inhibitors and angiotensin II receptor blockers should therefore not be used concomitantly in 
patients with diabetic nephropathy.

ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) was 
a study designed to test the benefit of adding aliskiren to a standard therapy of an ACE-inhibitor or an 
angiotensin II receptor blocker in patients with type 2 diabetes mellitus and chronic kidney disease, 
cardiovascular disease, or both. The study was terminated early because of an increased risk of adverse 
outcomes. Cardiovascular death and stroke were both numerically more frequent in the aliskiren group 
than in the placebo group and adverse events and serious adverse events of interest (hyperkalaemia, 
hypotension and renal dysfunction) were more frequently reported in the aliskiren group than in the 
placebo group.

Amlodipine
Amlodipine is a calcium ion influx inhibitor of the dihydropyridine group (slow channel blocker or 
calcium ion antagonist) and inhibits the transmembrane influx of calcium ions into cardiac and vascular 
smooth muscle. The mechanism of the antihypertensive action of amlodipine is due to a direct relaxant 
effect on vascular smooth muscle, leading to reductions in peripheral vascular resistance and in blood 
pressure. Experimental data indicate that amlodipine binds to both dihydropyridine and non-
dihydropyridine binding sites. Amlodipine is relatively vessel-selective, with a greater effect on vascular 
smooth muscle cells than on cardiac muscle cells.

In patients with hypertension, once daily dosing provides clinically significant reductions of blood 
pressure in both the supine and standing positions throughout the 24 hour interval. Due to the slow onset 
of action, acute hypotension is not a feature of amlodipine administration.
In hypertensive patients with normal renal function, therapeutic doses of amlodipine resulted in a 
decrease in renal vascular resistance and an increase in glomerular filtration rate and effective renal 
plasma flow, without change in filtration fraction or proteinuria.

Amlodipine has not been associated with any adverse metabolic effects or changes in plasma lipids and is 
suitable for use in patients with asthma, diabetes, and gout.

Use in patients with heart failure
Haemodynamic studies and exercise based controlled clinical trials in NYHA Class II-IV heart failure 
patients have shown that amlodipine did not lead to clinical deterioration as measured by exercise 
tolerance, left ventricular ejection fraction and clinical symptomatology.

A placebo controlled study (PRAISE) designed to evaluate patients in NYHA Class III-IV heart failure 
receiving digoxin, diuretics and ACE inhibitors has shown that amlodipine did not lead to an increase in 
risk of mortality or combined mortality and morbidity with heart failure.

In a follow-up, long term, placebo controlled study (PRAISE-2) of amlodipine in patients with NYHA III 
and IV heart failure without clinical symptoms or objective findings suggestive of underlying ischaemic 
disease, on stable doses of ACE inhibitors, digitalis, and diuretics, amlodipine had no effect on total 
cardiovascular mortality. In this same population amlodipine was associated with increased reports of 
pulmonary oedema.



73

Telmisartan/Amlodipine
In an 8-week multicenter, randomised, double-blind, placebo-controlled, parallel group factorial study in 
1461 patients with mild to severe hypertension (mean seated diastolic blood pressure ≥95 and 
≤119 mmHg), treatment with each combination dose of Twynsta resulted in significantly greater diastolic 
and systolic blood pressure reductions and higher control rates compared to the respective monotherapy 
components.

Twynsta showed dose-related reductions in systolic/diastolic blood pressure across the therapeutic dose 
range of 21.8/16.5 mmHg (40 mg/5 mg), 22.1/18.2 mmHg (80 mg/5 mg), 24.7/20.2 mmHg 
(40 mg/10 mg) and 26.4/20.1 mmHg (80 mg/10 mg). The reduction in diastolic blood pressure 
<90 mmHg was achieved in 71.6 %, 74.8 %, 82.1 %, 85.3 % of patients respectively. Values are adjusted 
for baseline and country.

The majority of the antihypertensive effect was attained within 2 weeks after initiation of therapy.
In a subset of 1050 patients with moderate to severe hypertension (DBP ≥100 mmHg) 32.7 – 51.8 %
responded sufficiently to monotherapy of either telmisartan or amlodipine. The observed mean changes 
in systolic/diastolic blood pressure with a combination therapy containing amlodipine 5 mg 
(22.2/17.2 mmHg with 40 mg/5 mg; 22.5/19.1 mmHg with 80 mg/5 mg) were comparable to or 
greater than those seen with amlodipine 10 mg (21.0/17.6 mmHg) and associated with significant 
lower oedema rates (1.4 % with 40 mg/5 mg; 0.5 % with 80 mg/5 mg; 17.6 % with amlodipine 10 mg).

Automated ambulatory blood pressure monitoring (ABPM) performed in a subset of 562 patients 
confirmed the results seen with in-clinic systolic and diastolic blood pressure reductions consistently 
over the entire 24-hours dosing period.

In a further multicentre, randomised, double-blind, active-controlled, parallel group study, a total of 1097 
patients with mild to severe hypertension who were not adequately controlled on amlodipine 5 mg 
received Twynsta (40 mg/5 mg or 80 mg/5 mg) or amlodipine alone (5 mg or 10 mg). After 8 weeks of 
treatment, each of the combinations was statistically significantly superior to both amlodipine 
monotherapy doses in reducing systolic and diastolic blood pressures (13.6/9.4 mmHg, 
15.0/10.6 mmHg with 40 mg/5 mg, 80 mg/5 mg versus 6.2/5.7 mmHg, 11.1/8.0 mmHg with 
amlodipine 5 mg and 10 mg and higher diastolic blood pressure control rates compared to the respective 
monotherapies were achieved (56.7 %, 63.8 % with 40 mg/5 mg and 80 mg/5 mg versus 42 %, 56.7 %
with amlodipine 5 mg and 10 mg). Oedema rates were significantly lower with 40 mg/5 mg and 
80 mg/5 mg compared to amlodipine 10 mg (4.4 % versus 24.9 %, respectively).

In another multicentre, randomised, double-blind, active-controlled, parallel group study, a total of 
947 patients with mild to severe hypertension who were not adequately controlled on amlodipine 10 mg 
received Twynsta (40 mg/10 mg or 80 mg/10 mg) or amlodipine alone (10 mg). After 8 weeks of 
treatment, each of the combination treatments was statistically significantly superior to amlodipine 
monotherapy in reducing diastolic and systolic blood pressure (11.1/9.2 mmHg, 11.3/ 9.3 mmHg 
with 40 mg/10 mg, 80 mg/10 mg versus 7.4/6.5 mmHg with amlodipine 10 mg) and higher diastolic 
blood pressure normalisation rates compared to monotherapy were achieved (63.7 %, 66.5 % with 
40 mg/10 mg, 80 mg/10 mg versus 51.1 % with amlodipine 10 mg).

In two corresponding open-label long-term follow up studies performed over a further 6 months the 
effect of Twynsta was maintained over the trial period. Furthermore it was shown that some patients not 
adequately controlled with Twynsta 40 mg/10 mg had additional blood pressure reduction by up-titration 
to Twynsta 80 mg/10 mg.

The overall incidence of adverse reactions with Twynsta in the clinical trial programme was low with 
only 12.7 % of patients on treatment experiencing adverse reactions. The most common adverse reactions 
were peripheral oedema and dizziness, see also section 4.8. The adverse reactions reported were in 
agreement with those anticipated from the safety profiles of the components telmisartan and amlodipine. 
No new or more severe adverse reactions were observed. The oedema related events (peripheral oedema, 



74

generalised oedema, and oedema) were consistently lower in patients who received Twynsta as compared 
to patients who received amlodipine 10 mg. In the factorial design trial the oedema rates were 1.3 % with 
Twynsta 40 mg/5 mg and 80 mg/5 mg, 8.8 % with Twynsta 40 mg/10 mg and 80 mg/10 mg and 18.4 %
with Amlodipine 10 mg. In patients not controlled on amlodipine 5 mg the oedema rates were 4.4 % for 
40 mg/5 mg and 80 mg/5 mg and 24.9 % for amlodipine 10 mg.

The antihypertensive effect of Twynsta was similar irrespective of age and gender, and was similar in 
patients with and without diabetes.

Twynsta has not been studied in any patient population other than hypertension. Telmisartan has been 
studied in a large outcome study in 25,620 patients with high cardiovascular risk (ONTARGET). 
Amlodipine has been studied in patients with chronic stable angina, vasospastic angina and 
angiographically documented coronary artery disease.

Paediatric population
The European Medicines Agency has waived the obligation to submit the results of studies with Twynsta
in all subsets of the paediatric population in hypertension (see section 4.2 for information on paediatric 
use).

5.2 Pharmacokinetic properties

Pharmacokinetic of the fixed dose combination 
The rate and extent of absorption of Twynsta are equivalent to the bioavailability of telmisartan and 
amlodipine when administered as individual tablets.

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

After oral administration of therapeutic doses, amlodipine is well absorbed with peak blood levels 
between 6-12 hours post dose. Absolute bioavailability has been estimated to be between 64 and 80 %. 
Amlodipine bioavailability is not affected by food ingestion.

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

The volume of distribution of amlodipine is approximately 21 l/kg. In vitro studies have shown that 
approximately 97.5 % of circulating amlodipine is bound to plasma proteins in hypertensive patients.

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

Amlodipine is extensively (approximatively 90 %) metabolised by the liver to inactive metabolites.

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



75

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

Amlodipine elimination from plasma is biphasic, with a terminal elimination half-life of approximately 
30 to 50 hours consistent with once daily dosing. Steady-state plasma levels are reached after continuous 
administration for 7–8 days. Ten per cent of original amlodipine and 60 % of amlodipine metabolites are 
excreted in urine. 

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

Amlodipine exhibits linear pharmacokinetics. 

Paediatric population (age below 18 years)
No pharmacokinetic data are available in the paediatric population.

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

Elderly
The pharmacokinetics of telmisartan do not differ in young and elderly patients.
The time to reach peak plasma concentrations of amlodipine is similar in elderly and younger subjects. In 
elderly patients, amlodipine clearance tends to decline with resulting increases in AUC and elimination 
half-life.

Renal impairment
In patients with mild to moderate and severe renal impairment, doubling of plasma concentrations of 
telmisartan 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 
subjects and cannot be removed by dialysis. The elimination half-life is not changed in patients with 
renal impairment. The pharmacokinetics of amlodipine are not significantly influenced by renal 
impairment.

Hepatic impairment
Pharmacokinetic studies in patients with hepatic impairment showed an increase in absolute 
bioavailability of telmisartan up to nearly 100 %. The elimination half-life of telmisartan is not changed 
in patients with hepatic impairment. Patients with hepatic insufficiency have decreased clearance of 
amlodipine with resulting increase of approximately 40-60 % in AUC.

5.3 Preclinical safety data

Since the non-clinical toxicity profiles of telmisartan and amlodipine are not overlapping, no 
exacerbation of toxicity was expected for the combination. This has been confirmed in a subchronic 
(13-week) toxicology study in rats, in which dose levels of 3.2/0.8, 10/2.5 and 40/10 mg/kg of telmisartan 
and amlodipine were tested.

Preclinical data available for the components of this fixed dose combination are reported below.

Telmisartan
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 



76

normotensive animals. In dogs, renal tubular dilation and atrophy were observed. Gastric mucosal injury 
(erosion, ulcers or inflammation) also was noted in rats and dogs. These pharmacologically-mediated 
undesirable effects, known from preclinical studies with both angiotensin converting enzyme inhibitors 
and angiotensin II receptor antagonists, were prevented by oral saline supplementation. In both species, 
increased plasma renin activity and hypertrophy/hyperplasia of the renal juxtaglomerular cells were 
observed. These changes, also a class effect of angiotensin converting enzyme inhibitors and other 
angiotensin II receptor antagonists, do not appear to have clinical significance.
No clear evidence of a teratogenic effect was observed, however at toxic dose levels of telmisartan an 
effect on the postnatal development of the offsprings such as lower body weight and delayed eye opening 
was observed.
There was no evidence of mutagenicity and relevant clastogenic activity in in vitro studies and no 
evidence of carcinogenicity in rats and mice.

Amlodipine

Reproductive toxicology
Reproductive studies in rats and mice have shown delayed date of delivery, prolonged duration of labour 
and decreased pup survival at dosages approximately 50 times greater than the maximum recommended 
dosage for humans based on mg/kg.

Impairment of fertility
There was no effect on the fertility of rats treated orally with amlodipine maleate (males for 64 days and 
females for 14 days prior to mating) at doses of up to 10 mg amlodipine/kg/day (about 8 times* the 
maximum recommended human dose of 10 mg/day on an mg/m2 basis). 
In another rat study in which male rats were treated with amlodipine besilate for 30 days at a dose 
comparable with the human dose based on mg/kg, decreased plasma follicle-stimulating hormone and 
testosterone were found as well as decreases in sperm density and in the number of mature spermatids 
and Sertoli cells.

Carcinogenesis, mutagenesis
Rats and mice treated with amlodipine in the diet for two years, at concentrations calculated to provide 
daily dosage levels of 0.5, 1.25, and 2.5 mg/kg/day showed no evidence of carcinogenicity. The highest 
dose (for mice, similar to, and for rats twice* the maximum recommended clinical dose of 10 mg on a 
mg/m2 basis) was close to the maximum tolerated dose for mice but not for rats.
Mutagenicity studies revealed no drug related effects at either the gene or chromosome levels.

*Based on patient weight of 50 kg

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Colloidal anhydrous silica
Brilliant blue FCF (E133)
Ferric oxide black (E172)
Ferric oxide yellow (E172)
Magnesium stearate
Maize starch
Meglumine
Microcrystalline cellulose
Povidone K25
Pregelatinised starch (prepared from maize starch)
Sodium hydroxide
Sorbitol (E420)



77

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years

6.4 Special precautions for storage

This medicinal product does not require any special temperature storage conditions.
Store in the original package in order to protect from light and moisture.
Remove the tablets from the blister only directly prior to intake.

6.5 Nature and contents of container

Aluminium/aluminium blisters (PA/Al/PVC/Al) in a carton containing 14, 28, 56, 98 tablets or 
aluminium/aluminium perforated unit dose blisters (PA/Al/PVC/Al) in a carton containing 30 x 1, 
90 x 1 tablets and multipacks containing 360 (4 packs of 90 x 1) tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

7. MARKETING AUTHORISATION HOLDER

Boehringer Ingelheim International GmbH
Binger Str. 173
D-55216 Ingelheim am Rhein
Germany

8. MARKETING AUTHORISATION NUMBERS

EU/1/10/648/022 (14 tablets)
EU/1/10/648/023 (28 tablets)
EU/1/10/648/024 (30 x 1 tablets)
EU/1/10/648/025 (56 tablets)
EU/1/10/648/026 (90 x 1 tablets)
EU/1/10/648/027 (98 tablets)
EU/1/10/648/028 (360 (4 x 90 x 1) tablets)

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 7 October 2010
Date of latest renewal: 20 August 2015

10. DATE OF REVISION OF THE TEXT

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

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


78

ANNEX II

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
AND USE 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORIZATION

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



79

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturer responsible for batch release

Boehringer Ingelheim Pharma GmbH & Co. KG
Binger Strasse 173
D-55216 Ingelheim am Rhein
Germany

Rottendorf Pharma GmbH
Ostenfelder Straße 51 - 61
D-59320 Ennigerloh
Germany

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

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

Medicinal product subject to medical prescription.

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING
AUTHORIZATION

 Periodic Safety Update Reports

The requirements for submission of periodic safety update reports for this medicinal product are set out 
in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal.

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

Not applicable.



80

ANNEX III

LABELLING AND PACKAGE LEAFLET



81

A. LABELLING



82

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

CARTON – 40 mg/5 mg

1. NAME OF THE MEDICINAL PRODUCT

Twynsta 40 mg/5 mg tablets
telmisartan/amlodipine

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 40 mg telmisartan and 5 mg amlodipine (as amlodipine besilate).

3. LIST OF EXCIPIENTS

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

4. PHARMACEUTICAL FORM AND CONTENTS

14 tablets
28 tablets
30 x 1 tablets
56 tablets
90 x 1 tablets
98 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 SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP 



83

9. SPECIAL STORAGE CONDITIONS

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

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Boehringer Ingelheim International GmbH
Binger Str. 173
D-55216 Ingelheim am Rhein
Germany

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/10/648/001 (14 tablets)
EU/1/10/648/002 (28 tablets)
EU/1/10/648/003 (30 x 1 tablets)
EU/1/10/648/004 (56 tablets)
EU/1/10/648/005 (90 x 1 tablets)
EU/1/10/648/006 (98 tablets)

13. BATCH NUMBER

Lot 

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Twynsta 40 mg/5 mg 

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC: {number} [product code]
SN: {number} [serial number]
NN: {number} [national reimbursement number or other national number identifying the medicinal 
product]



84

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

INTERMEDIATE CARTON OF THE MULTIPACKS OF 360 (4 PACKS OF 90 x 1
TABLETS) – WITHOUT BLUE BOX – 40 mg/5 mg

1. NAME OF THE MEDICINAL PRODUCT

Twynsta 40 mg/5 mg tablets
telmisartan/amlodipine

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 40 mg telmisartan and 5 mg amlodipine (as amlodipine besilate).

3. LIST OF EXCIPIENTS

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

4. PHARMACEUTICAL FORM AND CONTENTS

90 tablets
Component of a multipack, can't be sold separately.

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 SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP 

9. SPECIAL STORAGE CONDITIONS

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



85

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Boehringer Ingelheim International GmbH
Binger Str. 173
D-55216 Ingelheim am Rhein
Germany

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/10/648/007 (360 (4 x 90 x 1) tablets)

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Twynsta 40 mg/5 mg 

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC: {number} [product code]
SN: {number} [serial number]
NN: {number} [national reimbursement number or other national number identifying the medicinal 
product]



86

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

OUTER LABEL ON MULTIPACKS OF 360 (4 PACKS OF 90 x 1 TABLETS) BUNDLED –
INCLUDING THE BLUE BOX – 40 mg/5 mg

1. NAME OF THE MEDICINAL PRODUCT

Twynsta 40 mg/5 mg tablets
telmisartan/amlodipine

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 40 mg telmisartan and 5 mg amlodipine (as amlodipine besilate).

3. LIST OF EXCIPIENTS

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

4. PHARMACEUTICAL FORM AND CONTENTS

Multipack comprising 4 packs, each containing 90 x 1 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 SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP 

9. SPECIAL STORAGE CONDITIONS

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



87

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Boehringer Ingelheim International GmbH
Binger Str. 173
D-55216 Ingelheim am Rhein
Germany

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/10/648/007 (360 (4 x 90 x 1) tablets)

13. BATCH NUMBER

Lot 

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Twynsta 40 mg/5 mg 

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC: {number} [product code]
SN: {number} [serial number]
NN: {number} [national reimbursement number or other national number identifying the medicinal 
product]



88

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

Blister of 7 tablets – 40 mg/5 mg

1. NAME OF THE MEDICINAL PRODUCT

Twynsta 40 mg/5 mg tablets
telmisartan/amlodipine

2. NAME OF THE MARKETING AUTHORISATION HOLDER

Boehringer Ingelheim (Logo)

3. EXPIRY DATE

EXP 

4. BATCH NUMBER

Lot

5. OTHER



89

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

Unit dose blister of 10 tablets – 40 mg/5 mg

1. NAME OF THE MEDICINAL PRODUCT

Twynsta 40 mg/5 mg tablets
telmisartan/amlodipine

2. NAME OF THE MARKETING AUTHORISATION HOLDER

Boehringer Ingelheim (Logo)

3. EXPIRY DATE

EXP 

4. BATCH NUMBER

Lot

5. OTHER



90

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

CARTON – 40 mg/10 mg

1. NAME OF THE MEDICINAL PRODUCT

Twynsta 40 mg/10 mg tablets
telmisartan/amlodipine

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 40 mg telmisartan and 10 mg amlodipine (as amlodipine besilate).

3. LIST OF EXCIPIENTS

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

4. PHARMACEUTICAL FORM AND CONTENTS

14 tablets
28 tablets
30 x 1 tablets
56 tablets
90 x 1 tablets
98 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 SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP 



91

9. SPECIAL STORAGE CONDITIONS

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

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Boehringer Ingelheim International GmbH
Binger Str. 173
D-55216 Ingelheim am Rhein
Germany

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/10/648/008 (14 tablets)
EU/1/10/648/009 (28 tablets)
EU/1/10/648/010 (30 x 1 tablets)
EU/1/10/648/011 (56 tablets)
EU/1/10/648/012 (90 x 1 tablets)
EU/1/10/648/013 (98 tablets)

13. BATCH NUMBER

Lot 

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Twynsta 40 mg/10 mg 

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC: {number} [product code]
SN: {number} [serial number]
NN: {number} [national reimbursement number or other national number identifying the medicinal 
product]



92

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

INTERMEDIATE CARTON OF THE MULTIPACKS OF 360 (4 PACKS OF 90 x 1
TABLETS) – WITHOUT BLUE BOX – 40 mg/10 mg

1. NAME OF THE MEDICINAL PRODUCT

Twynsta 40 mg /10 mg tablets
telmisartan/amlodipine

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 40 mg telmisartan and 10 mg amlodipine (as amlodipine besilate).

3. LIST OF EXCIPIENTS

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

4. PHARMACEUTICAL FORM AND CONTENTS

90 tablets
Component of a multipack, can't be sold separately.

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 SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP 

9. SPECIAL STORAGE CONDITIONS

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



93

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Boehringer Ingelheim International GmbH
Binger Str. 173
D-55216 Ingelheim am Rhein
Germany

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/10/648/014 (360 (4 x 90 x 1) tablets)

13. BATCH NUMBER

Lot 

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Twynsta 40 mg/10 mg 

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC: {number} [product code]
SN: {number} [serial number]
NN: {number} [national reimbursement number or other national number identifying the medicinal 
product]



94

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

OUTER LABEL ON MULTIPACKS OF 360 (4 PACKS OF 90 x 1 TABLETS) BUNDLED –
INCLUDING THE BLUE BOX – 40 mg/10 mg

1. NAME OF THE MEDICINAL PRODUCT

Twynsta 40 mg/10 mg tablets
telmisartan/amlodipine

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 40 mg telmisartan and 10 mg amlodipine (as amlodipine besilate).

3. LIST OF EXCIPIENTS

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

4. PHARMACEUTICAL FORM AND CONTENTS

Multipack comprising 4 packs, each containing 90 x 1 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 SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP 

9. SPECIAL STORAGE CONDITIONS

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



95

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Boehringer Ingelheim International GmbH
Binger Str. 173
D-55216 Ingelheim am Rhein
Germany

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/10/648/014 (360 (4 x 90 x 1) tablets)

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Twynsta 40 mg/10 mg 

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC: {number} [product code]
SN: {number} [serial number]
NN: {number} [national reimbursement number or other national number identifying the medicinal 
product]



96

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

Blister of 7 tablets – 40 mg/10 mg

1. NAME OF THE MEDICINAL PRODUCT

Twynsta 40 mg/10 mg tablets
telmisartan/amlodipine

2. NAME OF THE MARKETING AUTHORISATION HOLDER

Boehringer Ingelheim (Logo)

3. EXPIRY DATE

EXP 

4. BATCH NUMBER

Lot

5. OTHER



97

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

Unit dose blister of 10 tablets – 40 mg/10 mg

1. NAME OF THE MEDICINAL PRODUCT

Twynsta 40 mg/10 mg tablets
telmisartan/amlodipine

2. NAME OF THE MARKETING AUTHORISATION HOLDER

Boehringer Ingelheim (Logo)

3. EXPIRY DATE

EXP 

4. BATCH NUMBER

Lot

5. OTHER



98

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

CARTON – 80 mg/5 mg

1. NAME OF THE MEDICINAL PRODUCT

Twynsta 80 mg/5 mg tablets
telmisartan/amlodipine

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 80 mg telmisartan and 5 mg amlodipine (as amlodipine besilate).

3. LIST OF EXCIPIENTS

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

4. PHARMACEUTICAL FORM AND CONTENTS

14 tablets
28 tablets
30 x 1 tablets
56 tablets
90 x 1 tablets
98 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 SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP 



99

9. SPECIAL STORAGE CONDITIONS

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

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Boehringer Ingelheim International GmbH
Binger Str. 173
D-55216 Ingelheim am Rhein
Germany

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/10/648/015 (14 tablets)
EU/1/10/648/016 (28 tablets)
EU/1/10/648/017 (30 x 1 tablets)
EU/1/10/648/018 (56 tablets)
EU/1/10/648/019 (90 x 1 tablets)
EU/1/10/648/020 (98 tablets)

13. BATCH NUMBER

Lot 

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Twynsta 80 mg/5 mg 

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC: {number} [product code]
SN: {number} [serial number]
NN: {number} [national reimbursement number or other national number identifying the medicinal 
product]



100

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

INTERMEDIATE CARTON OF THE MULTIPACKS OF 360 (4 PACKS OF 90 x 1
TABLETS) – WITHOUT BLUE BOX – 80 mg/5 mg

1. NAME OF THE MEDICINAL PRODUCT

Twynsta 80 mg/5 mg tablets
telmisartan/amlodipine

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 80 mg telmisartan and 5 mg amlodipine (as amlodipine besilate).

3. LIST OF EXCIPIENTS

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

4. PHARMACEUTICAL FORM AND CONTENTS

90 tablets
Component of a multipack, can't be sold separately.

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 SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP 

9. SPECIAL STORAGE CONDITIONS

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



101

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Boehringer Ingelheim International GmbH
Binger Str. 173
D-55216 Ingelheim am Rhein
Germany

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/10/648/021 (360 (4 x 90 x 1) tablets)

13. BATCH NUMBER

Lot 

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Twynsta 80 mg/5 mg 

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC: {number} [product code]
SN: {number} [serial number]
NN: {number} [national reimbursement number or other national number identifying the medicinal 
product]



102

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

OUTER LABEL ON MULTIPACKS OF 360 (4 PACKS OF 90 x 1 TABLETS) BUNDLED –
INCLUDING THE BLUE BOX – 80 mg/5 mg

1. NAME OF THE MEDICINAL PRODUCT

Twynsta 80 mg/5 mg tablets
telmisartan/amlodipine

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 80 mg telmisartan and 5 mg amlodipine (as amlodipine besilate).

3. LIST OF EXCIPIENTS

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

4. PHARMACEUTICAL FORM AND CONTENTS

Multipack comprising 4 packs, each containing 90 x 1 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 SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP 

9. SPECIAL STORAGE CONDITIONS

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



103

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Boehringer Ingelheim International GmbH
Binger Str. 173
D-55216 Ingelheim am Rhein
Germany

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/10/648/021 (360 (4 x 90 x 1) tablets)

13. BATCH NUMBER

Lot 

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Twynsta 80 mg/5 mg 

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC: {number} [product code]
SN: {number} [serial number]
NN: {number} [national reimbursement number or other national number identifying the medicinal 
product]



104

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

Blister of 7 tablets – 80 mg/5 mg

1. NAME OF THE MEDICINAL PRODUCT

Twynsta 80 mg/5 mg tablets
telmisartan/amlodipine

2. NAME OF THE MARKETING AUTHORISATION HOLDER

Boehringer Ingelheim (Logo)

3. EXPIRY DATE

EXP 

4. BATCH NUMBER

Lot

5. OTHER



105

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

Unit dose blister of 10 tablets – 80 mg/5 mg

1. NAME OF THE MEDICINAL PRODUCT

Twynsta 80 mg/5 mg tablets
telmisartan/amlodipine

2. NAME OF THE MARKETING AUTHORISATION HOLDER

Boehringer Ingelheim (Logo)

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER



106

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

CARTON – 80 mg/10 mg

1. NAME OF THE MEDICINAL PRODUCT

Twynsta 80 mg/10 mg tablets
telmisartan/amlodipine

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 80 mg telmisartan and 10 mg amlodipine (as amlodipine besilate).

3. LIST OF EXCIPIENTS

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

4. PHARMACEUTICAL FORM AND CONTENTS

14 tablets
28 tablets
30 x 1 tablets
56 tablets
90 x 1 tablets
98 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 SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP 



107

9. SPECIAL STORAGE CONDITIONS

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

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Boehringer Ingelheim International GmbH
Binger Str. 173
D-55216 Ingelheim am Rhein
Germany

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/10/648/022 (14 tablets)
EU/1/10/648/023 (28 tablets)
EU/1/10/648/024 (30 x 1 tablets)
EU/1/10/648/025 (56 tablets)
EU/1/10/648/026 (90 x 1 tablets)
EU/1/10/648/027 (98 tablets)

13. BATCH NUMBER

Lot 

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Twynsta 80 mg/10 mg 

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC: {number} [product code]
SN: {number} [serial number]
NN: {number} [national reimbursement number or other national number identifying the medicinal 
product]



108

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

INTERMEDIATE CARTON OF THE MULTIPACKS OF 360 (4 PACKS OF 90 x 1
TABLETS) – WITHOUT BLUE BOX – 80 mg/10 mg

1. NAME OF THE MEDICINAL PRODUCT

Twynsta 80 mg/10 mg tablets
telmisartan/amlodipine

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 80 mg telmisartan and 10 mg amlodipine (as amlodipine besilate).

3. LIST OF EXCIPIENTS

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

4. PHARMACEUTICAL FORM AND CONTENTS

90 tablets
Component of a multipack, can't be sold separately.

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 SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP 

9. SPECIAL STORAGE CONDITIONS

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



109

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Boehringer Ingelheim International GmbH
Binger Str. 173
D-55216 Ingelheim am Rhein
Germany

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/10/648/028 (360 (4 x 90 x 1) tablets)

13. BATCH NUMBER

Lot 

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Twynsta 80 mg/10 mg 

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC: {number} [product code]
SN: {number} [serial number]
NN: {number} [national reimbursement number or other national number identifying the medicinal 
product]



110

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

OUTER LABEL ON MULTIPACKS OF 360 (4 PACKS OF 90 x 1 TABLETS) BUNDLED –
INCLUDING THE BLUE BOX – 80 mg/10 mg

1. NAME OF THE MEDICINAL PRODUCT

Twynsta 80 mg/10 mg tablets
telmisartan/amlodipine

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 80 mg telmisartan and 10 mg amlodipine (as amlodipine besilate).

3. LIST OF EXCIPIENTS

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

4. PHARMACEUTICAL FORM AND CONTENTS

Multipack comprising 4 packs, each containing 90 x 1 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 SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP 

9. SPECIAL STORAGE CONDITIONS

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



111

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Boehringer Ingelheim International GmbH
Binger Str. 173
D-55216 Ingelheim am Rhein
Germany

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/10/648/028 (360 (4 x 90 x 1) tablets)

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Twynsta 80 mg/10 mg 

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC: {number} [product code]
SN: {number} [serial number]
NN: {number} [national reimbursement number or other national number identifying the medicinal 
product]



112

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

Blister of 7 tablets – 80 mg/10 mg

1. NAME OF THE MEDICINAL PRODUCT

Twynsta 80 mg/10 mg tablets
telmisartan/amlodipine

2. NAME OF THE MARKETING AUTHORISATION HOLDER

Boehringer Ingelheim (Logo)

3. EXPIRY DATE

EXP 

4. BATCH NUMBER

Lot

5. OTHER



113

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

Unit dose blister of 10 tablets – 80 mg/10 mg

1. NAME OF THE MEDICINAL PRODUCT

Twynsta 80 mg/10 mg tablets
telmisartan/amlodipine

2. NAME OF THE MARKETING AUTHORISATION HOLDER

Boehringer Ingelheim (Logo)

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER



114

B. PACKAGE LEAFLET



115

Package leaflet: Information for the user
Twynsta 40 mg/5 mg tablets

Telmisartan/Amlodipine

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

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

effects not listed in this leaflet. See section 4.

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

1. What Twynsta is and what it is used for

Twynsta tablets contain two active substances called telmisartan and amlodipine. Both of these 
substances help to control your high blood pressure:
 Telmisartan belongs to a group of substances called “angiotensin-II receptor antagonists”.

Angiotensin II is a substance produced in the body which causes blood vessels to narrow, thus 
increasing blood pressure. Telmisartan works by blocking the effect of angiotensin II.

 Amlodipine belongs to a group of substances called “calcium channel blockers”. Amlodipine stops
calcium from moving into the blood vessel wall which stops the blood vessels from tightening.

This means that both of these active substances work together to help stop your blood vessels tightening. 
As a result, the blood vessels relax and blood pressure is lowered.

Twynsta is used to treat high blood pressure
 in adult patients whose blood pressure is not controlled enough with amlodipine alone.
 in adult patients who already receive telmisartan and amlodipine from separate tablets and who

wish to take instead the same doses in one tablet for convenience.

High blood pressure, if not treated, can damage blood vessels in several organs, which puts patients at 
risk of serious events such as heart attack, heart or kidney failure, stroke, or blindness. There are usually 
no symptoms of high blood pressure before damage occurs. Thus it is important to regularly measure 
blood pressure to verify if it is within the normal range.

2. What you need to know before you take Twynsta

Do not take Twynsta
 if you are allergic to telmisartan or amlodipine or any of the other ingredients of this medicine 

(listed in section 6).
 if you are allergic to other medicines of the dihydropyridine type (one type of calcium channel 

blocker).
 if you are more than 3 months pregnant. (It is also better to avoid Twynsta in early pregnancy – see 

Pregnancy section.)



116

 if you have severe liver problems or biliary obstruction (problems with drainage of the bile from 
the liver and gall bladder).

 if you have narrowing of the aortic heart valve (aortic stenosis) or cardiogenic shock (a condition 
where your heart is unable to supply enough blood to the body). 

 if you suffer from heart failure after a heart attack.
 if you have diabetes or impaired kidney function and you are treated with a blood pressure 

lowering medicine containing aliskiren.

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

Warnings and precautions
Talk to your doctor before taking Twynsta if you are suffering or have ever suffered from any of the 
following conditions or illnesses:
 Kidney disease or kidney transplant.
 Narrowing of the blood vessels to one or both kidneys (renal artery stenosis).
 Liver disease.
 Heart trouble.
 Raised aldosterone levels (which lead to 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.
 Narrowing of the aorta (aortic stenosis).
 Heart-associated chest pain also at rest or with minimal effort (unstable angina pectoris).
 A heart attack within the last four weeks.

Talk to your doctor before taking Twynsta:
 if you are taking any of the following medicines used to treat high blood pressure:

- an ACE-inhibitor (for example enalapril, lisinopril, ramipril), in particular if you have diabetes-
related kidney problems.
- aliskiren.
Your doctor may check your kidney function, blood pressure, and the amount of electrolytes (e.g. 
potassium) in your blood at regular intervals. See also “Do not take Twynsta”.

 if you are elderly and your dose needs to be increased.

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

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

Other medicines and Twynsta
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. 
Your doctor may need to change the dose of these other medicines or take other precautions. In some 
cases you may have to stop taking one of the medicines. This applies especially to the medicines listed 
below:
 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’).
 Angiotensin II receptor antagonists.
 ACE-inhibitors or aliskiren (see also information under the headings “Do not take Twynsta” and 

“Warnings and precautions”).



117

 NSAIDs (non steroidal anti-inflammatory medicines, e.g. acetylsalicylic acid or ibuprofen), 
heparin, immunosuppressives (e.g. cyclosporin or tacrolimus), and the antibiotic trimethoprim.

 Rifampicin, erythromycin, clarithromycin (antibiotics).
 St. John’s wort.
 Dantrolene (infusion for severe body temperature abnormalities).
 Medicines used to alter the way your immune system works (e.g. sirolimus, temsirolimus and 

everolimus).
 Medicines used for HIV/AIDS (e.g. ritonavir) or for treatment of fungal infections (e.g. 

ketoconazole).
 Diltiazem (cardiac medicine).
 Simvastatin to treat elevated levels of cholesterol.
 Digoxin.

As with other blood pressure lowering medicines, the effect of Twynsta may be reduced when you take 
NSAIDs (non steroidal anti-inflammatory medicines, e.g. acetylsalicylic acid or ibuprofen) or 
corticosteroids.

Twynsta may increase the blood pressure lowering effect of other medicines used to treat high blood 
pressure or of medicines with blood pressure lowering potential (e.g. baclofen, amifostine, neuroleptics 
or antidepressants).

Twynsta with food and drink
Low blood pressure may be aggravated by alcohol. You may notice this as dizziness when standing up.

Grapefruit juice and grapefruit should not be consumed when you take Twynsta. This is because 
grapefruit and grapefruit juice may lead to increased blood levels of the active ingredient amlodipine in 
some patients and may increase the blood pressure lowering effect of Twynsta.

Pregnancy and breast-feeding
Pregnancy
You must tell your doctor if you think you might be pregnant or are planning to have a baby. Your doctor 
will normally advise you to stop taking Twynsta before you become pregnant or as soon as you know you 
are pregnant and will advise you to take another medicine instead of Twynsta. Twynsta 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
Amlodipine has been shown to pass into breast milk in small amounts.
Tell your doctor if you are breast-feeding or about to start breast-feeding. Twynsta 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.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines
Some people may experience side effects such as fainting, sleepiness, dizziness or a feeling of spinning 
(vertigo) when they are treated for high blood pressure. If you experience these side effects, do not drive 
or use machines.

Twynsta contains sorbitol 
This medicine contains 168.64 mg sorbitol in each tablet.

Twynsta contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-
free’.



118

3. How to take Twynsta

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

The recommended dose is one tablet a day. Try to take the tablet at the same time each day.
Remove your Twynsta tablet from the blister only directly prior to intake.

You can take Twynsta with or without food. The tablets should be swallowed with some water or other 
non-alcoholic drink.

If your liver is not working properly, the usual dose should not exceed one 40 mg/5 mg tablet or 
one 40 mg/10 mg tablet per day.

If you take more Twynsta than you should
If you accidentally take too many tablets, contact your doctor, pharmacist, or your nearest hospital 
emergency department immediately. You might experience low blood pressure and rapid heart beat. Slow 
heart beat, dizziness, reduced kidney function including kidney failure, marked and prolonged low blood 
pressure including shock and death have also been reported.

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

If you stop taking Twynsta
It is important that you take Twynsta every day until your doctor tells you otherwise. If you have the 
impression that the effect of Twynsta 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, this medicine can cause side effects, although not everybody gets them. 

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

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

Sepsis (often called "blood poisoning", is a severe infection of the whole-body with high fever and the 
feeling of being severely ill), rapid swelling of the skin and mucosa (angioedema); these side effects are 
rare (may affect up to 1 in 1,000 people) but are extremely serious and patients should stop taking the 
medicine and see their doctor immediately. If these effects are not treated they could be fatal. Increased 
incidence of sepsis has been observed with telmisartan only, however can not be ruled out for Twynsta.

Common side effects (may affect up to 1 in 10 people):
Dizziness, ankle swelling (oedema).



119

Uncommon side effects (may affect up to 1 in 100 people):
Sleepiness, migraine, headache, tingling or numbness of the hands or feet, feeling of spinning (vertigo), 
slow heart rate, palpitations (awareness of your heart beat), low blood pressure (hypotension), dizziness 
on standing up (orthostatic hypotension), flushing, cough, stomach ache (abdominal pain), diarrhoea, 
feeling sick (nausea), itching, joint pain, muscle cramps, muscle pain, inability to obtain an erection, 
weakness, chest pain, tiredness, swelling (oedema), increased levels of hepatic enzymes.

Rare side effects (may affect up to 1 in 1,000 people):
Urinary bladder infection, feeling sad (depression), feeling anxious, sleeplessness, fainting, nerve 
damage in the hands or feet, reduced sense of touch, taste abnormalities, trembling, vomiting, enlarged 
gums, discomfort in the abdomen, dry mouth, eczema (a skin disorder), redness of skin, rash, back pain, 
leg pain, urge to urinate during the night, feeling unwell (malaise), increased levels of uric acid in the 
blood.

Very rare side effect (may affect up to 1 in 10,000 people):
Progressive scarring of lung tissue (interstitial lung disease [mainly pneumonia of the interstitium and 
pneumonia with excess eosinophils])

The following side effects have been observed with the components telmisartan or amlodipine and may 
occur also with Twynsta:

Telmisartan
In patients taking telmisartan alone the following additional side effects have been reported:

Uncommon side effects (may affect up to 1 in 100 people): 
Urinary tract infections, upper respiratory tract infections (e.g. sore throat, inflamed sinuses, common 
cold), deficiency in red blood cells (anaemia), high potassium levels in the blood, shortness of breath, 
bloating, increased sweating, kidney damage including sudden inability of the kidneys to work, increased 
levels of creatinine.

Rare side effects (may affect up to 1 in 1,000 people):
Increase in certain white blood cells (eosinophilia), low platelet count (thrombocytopenia), allergic 
reaction (e.g. rash, itching, difficulty of breathing, wheezing, swelling of the face or low blood pressure),
low blood sugar levels (in diabetic patients), impaired vision, fast heart beat, upset stomach, abnormal 
liver function, hives (urticaria), medicine rash, inflammation of the tendons, flu-like illness (for example 
muscle pain, feeling generally unwell), decreased haemoglobin (a blood protein), increased levels of 
creatinine phosphokinase in the blood.
Most cases of abnormal liver function and liver disorder from post-marketing experience with telmisartan 
occurred in Japanese patients. Japanese patients are more likely to experience this side effect.

Amlodipine
In patients taking amlodipine alone the following additional side effects have been reported:

Common side effects (may affect up to 1 in 10 people):
Altered bowel habits, diarrhoea, constipation, visual disturbances, double vision, ankle swelling. 

Uncommon side effects (may affect up to 1 in 100 people):
Mood changes, impaired vision, ringing in the ears, shortness of breath, sneezing/running nose, hair loss, 
unusual bruising and bleeding (red blood cell damage), skin discolouration, increased sweating, difficulty 
passing urine, increased need to pass urine especially at night, enlarging of male breasts, pain, weight 
increased, weight decreased.

Rare side effects (may affect up to 1 in 1,000 people): 
Confusion.



120

Very rare side effects (may affect up to 1 in 10,000 people):
Reduced number of white blood cells (leucopenia), low platelet count (thrombocytopenia), allergic 
reaction (e.g. rash, itching, difficulty breathing, wheezing, swelling of the face or low blood pressure), 
excess sugar in blood , uncontrollable twitching or jerking movements, heart attack, irregular heart beat, 
inflammation of the blood vessels, inflamed pancreas, inflammation of the stomach lining (gastritis), 
inflammation of the liver, yellowing of the skin (jaundice), increased levels of hepatic enzymes with 
jaundice, rapid swelling of skin and mucosa (angioedema), severe skin reactions, hives (urticaria), severe 
allergic reactions with blistering eruptions of the skin and mucous membranes (exfoliative dermatitis, 
Stevens-Johnson-Syndrome), increased sensitivity of the skin to sun, increased muscle tension.

Not known (frequency cannot be estimated from the available data):
Severe allergic reactions with blistering eruptions of the skin and mucous membranes (toxic epidermal 
necrolysis).

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not 

listed in this leaflet. You can also report side effects directly via the national reporting system listed in 

Appendix V. By reporting side effects you can help provide more information on the safety of this 

medicine.

5. How to store Twynsta

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

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

This medicine does not require any special temperature storage conditions. Store in the original package 
in order to protect from light and moisture. Remove your Twynsta tablet from the blister only directly 
prior to intake.

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

6. Contents of the pack and other information

What Twynsta contains
 The active substances are telmisartan and amlodipine. 

Each tablet contains 40 mg telmisartan and 5 mg amlodipine (as amlodipine besilate).

 The other ingredients are colloidal anhydrous silica, brilliant blue FCF (E133), ferric oxide black 
(E172), ferric oxide yellow (E172), magnesium stearate, maize starch, meglumine, 
microcrystalline cellulose, povidone K25, pregelatinized starch prepared from maize starch, 
sodium hydroxide, sorbitol (E420).

What Twynsta looks like and contents of the pack
Twynsta 40 mg/5 mg tablets are blue and white oval shaped two layer tablets engraved with the product 
code A1 and the company logo on the white layer.

Twynsta is available in a folding box containing 14, 28, 56, 98 tablets in aluminium/aluminium blisters 
or containing 30 x 1, 90 x 1, 360 (4 x 90 x 1) tablets in aluminium/aluminium perforated unit dose 
blisters.

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


121

Not all pack sizes may be marketed.

Marketing Authorisation Holder Manufacturer
Boehringer Ingelheim International GmbH
Binger Str. 173
D-55216 Ingelheim am Rhein
Germany

Boehringer Ingelheim Pharma GmbH & Co. KG
Binger Str. 173
D-55216 Ingelheim am Rhein
Germany

Rottendorf Pharma GmbH
Ostenfelder Straße 51 - 61
D-59320 Ennigerloh
Germany



122

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

België/Belgique/Belgien
SCS Boehringer Ingelheim Comm.V
Tél/Tel: +32 2 773 33 11

Lietuva
Boehringer Ingelheim RCV GmbH & Co KG 
Lietuvos filialas
Tel.: +370 37 473922

България
Бьорингер Ингелхайм РЦВ ГмбХ и Ко КГ -
клон България
Тел: +359 2 958 79 98

Luxembourg/Luxemburg
SCS Boehringer Ingelheim Comm.V
Tél/Tel: +32 2 773 33 11

Česká republika
Boehringer Ingelheim spol. s r.o.
Tel: +420 234 655 111

Magyarország
Boehringer Ingelheim RCV GmbH & Co KG
Magyarországi Fióktelepe
Tel.: +36 1 299 89 00

Danmark
Boehringer Ingelheim Danmark A/S
Tlf: +45 39 15 88 88

Malta
Boehringer Ingelheim Ireland Ltd.
Tel: +353 1 295 9620

Deutschland
Boehringer Ingelheim Pharma GmbH & Co. KG
Tel: +49 (0) 800 77 90 900

Nederland
Boehringer Ingelheim b.v.
Tel: +31 (0) 800 22 55 889

Eesti
Boehringer Ingelheim RCV GmbH & Co KG
Eesti Filiaal
Tel: +372 612 8000

Norge
Boehringer Ingelheim Norway KS
Tlf: +47 66 76 13 00

Ελλάδα
Boehringer Ingelheim Ellas A.E.
Tηλ: +30 2 10 89 06 300

Österreich
Boehringer Ingelheim RCV GmbH & Co KG
Tel: +43 1 80 105-7870

España
Boehringer Ingelheim España, S.A.
Tel: +34 93 404 51 00

Polska
Boehringer Ingelheim Sp.zo.o.
Tel.: +48 22 699 0 699

France
Boehringer Ingelheim France S.A.S.
Tél: +33 3 26 50 45 33

Portugal
Boehringer Ingelheim, Unipessoal, Lda.
Tel: +351 21 313 53 00

Hrvatska
Boehringer Ingelheim Zagreb d.o.o.
Tel: +385 1 2444 600

România
Boehringer Ingelheim RCV GmbH & Co KG
Viena - Sucursala Bucuresti
Tel: +40 21 302 2800

Ireland
Boehringer Ingelheim Ireland Ltd.
Tel: +353 1 295 9620

Slovenija
Boehringer Ingelheim RCV GmbH & Co KG
Podružnica Ljubljana
Tel: +386 1 586 40 00



123

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Boehringer Ingelheim RCV GmbH & Co KG
organizačná zložka
Tel: +421 2 5810 1211

Italia
Boehringer Ingelheim Italia S.p.A.
Tel: +39 02 5355 1

Suomi/Finland
Boehringer Ingelheim Finland Ky
Puh/Tel: +358 10 3102 800

Κύπρος
Boehringer Ingelheim Ellas A.E.
Tηλ: +30 2 10 89 06 300

Sverige
Boehringer Ingelheim AB
Tel: +46 8 721 21 00

Latvija
Boehringer Ingelheim RCV GmbH & Co KG
Latvijas filiāle
Tel: +371 67 240 011

United Kingdom
Boehringer Ingelheim Ltd.
Tel: +44 1344 424 600

This leaflet was last revised in 

Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/.

http://www.emea.europa.eu


124

Package leaflet: Information for the user
Twynsta 40 mg/10 mg tablets

Telmisartan/Amlodipine

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

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

effects not listed in this leaflet. See section 4.

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

1. What Twynsta is and what it is used for

Twynsta tablets contain two active substances called telmisartan and amlodipine. Both of these 
substances help to control your high blood pressure:
 Telmisartan belongs to a group of substances called “angiotensin-II receptor antagonists”. 

Angiotensin II is a substance produced in the body which causes blood vessels to narrow, thus 
increasing blood pressure. Telmisartan works by blocking the effect of angiotensin II.

 Amlodipine belongs to a group of substances called “calcium channel blockers”. Amlodipine stops 
calcium from moving into the blood vessel wall which stops the blood vessels from tightening.

This means that both of these active substances work together to help stop your blood vessels tightening. 
As a result, the blood vessels relax and blood pressure is lowered.

Twynsta is used to treat high blood pressure
 in adult patients whose blood pressure is not controlled enough with amlodipine alone.
 in adult patients who already receive telmisartan and amlodipine from separate tablets and who 

wish to take instead the same doses in one tablet for convenience.

High blood pressure, if not treated, can damage blood vessels in several organs, which puts patients at 
risk of serious events such as heart attack, heart or kidney failure, stroke, or blindness. There are usually 
no symptoms of high blood pressure before damage occurs. Thus it is important to regularly measure 
blood pressure to verify if it is within the normal range.

2. What you need to know before you take Twynsta

Do not take Twynsta
 if you are allergic to telmisartan or amlodipine or any of the other ingredients of this medicine 

(listed in section 6).
 if you are allergic to other medicines of the dihydropyridine type (one type of calcium channel 

blocker).
 if you are more than 3 months pregnant. (It is also better to avoid Twynsta in early pregnancy – see 

Pregnancy section.)



125

 if you have severe liver problems or biliary obstruction (problems with drainage of the bile from 
the liver and gall bladder).

 if you have narrowing of the aortic heart valve (aortic stenosis) or cardiogenic shock (a condition 
where your heart is unable to supply enough blood to the body). 

 if you suffer from heart failure after a heart attack.
 if you have diabetes or impaired kidney function and you are treated with a blood pressure 

lowering medicine containing aliskiren.

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

Warnings and precautions
Talk to your doctor before taking Twynsta if you are suffering or have ever suffered from any of the 
following conditions or illnesses:
 Kidney disease or kidney transplant.
 Narrowing of the blood vessels to one or both kidneys (renal artery stenosis).
 Liver disease.
 Heart trouble.
 Raised aldosterone levels (which lead to 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.
 Narrowing of the aorta (aortic stenosis).
 Heart-associated chest pain also at rest or with minimal effort (unstable angina pectoris).
 A heart attack within the last four weeks.

Talk to your doctor before taking Twynsta:
 if you are taking any of the following medicines used to treat high blood pressure:

- an ACE-inhibitor (for example enalapril, lisinopril, ramipril), in particular if you have diabetes-
related kidney problems.
- aliskiren.
Your doctor may check your kidney function, blood pressure, and the amount of electrolytes (e.g. 
potassium) in your blood at regular intervals. See also “Do not take Twynsta”.

 if you are elderly and your dose needs to be increased.

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

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

Other medicines and Twynsta
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. 
Your doctor may need to change the dose of these other medicines or take other precautions. In some 
cases you may have to stop taking one of the medicines. This applies especially to the medicines listed 
below:
 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’).
 Angiotensin II receptor antagonists.
 ACE-inhibitors or aliskiren (see also information under the headings “Do not take Twynsta” and 

“Warnings and precautions”).



126

 NSAIDs (non steroidal anti-inflammatory medicines, e.g. acetylsalicylic acid or ibuprofen), 
heparin, immunosuppressives (e.g. cyclosporin or tacrolimus), and the antibiotic trimethoprim.

 Rifampicin, erythromycin, clarithromycin (antibiotics).
 St. John’s wort.
 Dantrolene (infusion for severe body temperature abnormalities).
 Medicines used to alter the way your immune system works (e.g. sirolimus, temsirolimus and 

everolimus).
 Medicines used for HIV/AIDS (e.g. ritonavir) or for treatment of fungal infections (e.g. 

ketoconazole).
 Diltiazem (cardiac medicine).
 Simvastatin to treat elevated levels of cholesterol.
 Digoxin.

As with other blood pressure lowering medicines, the effect of Twynsta may be reduced when you take 
NSAIDs (non steroidal anti-inflammatory medicines, e.g. acetylsalicylic acid or ibuprofen) or 
corticosteroids.

Twynsta may increase the blood pressure lowering effect of other medicines used to treat high blood 
pressure or of medicines with blood pressure lowering potential (e.g. baclofen, amifostine, neuroleptics 
or antidepressants).

Twynsta with food and drink
Low blood pressure may be aggravated by alcohol. You may notice this as dizziness when standing up.

Grapefruit juice and grapefruit should not be consumed when you take Twynsta. This is because 
grapefruit and grapefruit juice may lead to increased blood levels of the active ingredient amlodipine in 
some patients and may increase the blood pressure lowering effect of Twynsta.

Pregnancy and breast-feeding
Pregnancy
You must tell your doctor if you think you might be pregnant or are planning to have a baby. Your doctor 
will normally advise you to stop taking Twynsta before you become pregnant or as soon as you know you 
are pregnant and will advise you to take another medicine instead of Twynsta. Twynsta 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
Amlodipine has been shown to pass into breast milk in small amounts.
Tell your doctor if you are breast-feeding or about to start breast-feeding. Twynsta 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.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines
Some people may experience side effects such as fainting, sleepiness, dizziness or a feeling of spinning 
(vertigo) when they are treated for high blood pressure. If you experience these side effects, do not drive 
or use machines.

Twynsta contains sorbitol 
This medicine contains 168.64 mg sorbitol in each tablet.

Twynsta contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-
free’.



127

3. How to take Twynsta

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

The recommended dose is one tablet a day. Try to take the tablet at the same time each day.
Remove your Twynsta tablet from the blister only directly prior to intake.

You can take Twynsta with or without food. The tablets should be swallowed with some water or other 
non-alcoholic drink.

If your liver is not working properly, the usual dose should not exceed one 40 mg/5 mg tablet or one 40 
mg/10 mg tablet per day.

If you take more Twynsta than you should
If you accidentally take too many tablets, contact your doctor, pharmacist, or your nearest hospital 
emergency department immediately. You might experience low blood pressure and rapid heart beat. Slow 
heart beat, dizziness, reduced kidney function including kidney failure, marked and prolonged low blood 
pressure including shock and death have also been reported.

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

If you stop taking Twynsta
It is important that you take Twynsta every day until your doctor tells you otherwise. If you have the 
impression that the effect of Twynsta 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, this medicine can cause side effects, although not everybody gets them. 

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

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

Sepsis (often called "blood poisoning", is a severe infection of the whole-body with high fever and the 
feeling of being severely ill), rapid swelling of the skin and mucosa (angioedema); these side effects are 
rare (may affect up to 1 in 1,000 people) but are extremely serious and patients should stop taking the 
medicine and see their doctor immediately. If these effects are not treated they could be fatal. Increased 
incidence of sepsis has been observed with telmisartan only, however can not be ruled out for Twynsta.

Common side effects (may affect up to 1 in 10 people): 
Dizziness, ankle swelling (oedema).

Uncommon side effects (may affect up to 1 in 100 people): 
Sleepiness, migraine, headache, tingling or numbness of the hands or feet, feeling of spinning (vertigo), 
slow heart rate, palpitations (awareness of your heart beat), low blood pressure (hypotension), dizziness 
on standing up (orthostatic hypotension), flushing, cough, stomach ache (abdominal pain), diarrhoea, 



128

feeling sick (nausea), itching, joint pain, muscle cramps, muscle pain, inability to obtain an erection, 
weakness, chest pain, tiredness, swelling (oedema), increased levels of hepatic enzymes.

Rare side effects (may affect up to 1 in 1,000 people): 
Urinary bladder infection, feeling sad (depression), feeling anxious, sleeplessness, fainting, nerve 
damage in the hands or feet, reduced sense of touch, taste abnormalities, trembling, vomiting, enlarged 
gums, discomfort in the abdomen, dry mouth, eczema (a skin disorder), redness of skin, rash, back pain, 
leg pain, urge to urinate during the night, feeling unwell (malaise), increased levels of uric acid in the 
blood.

Very rare side effect (may affect up to 1 in 10,000 people):
Progressive scarring of lung tissue (interstitial lung disease [mainly pneumonia of the interstitium and 
pneumonia with excess eosinophils])

The following side effects have been observed with the components telmisartan or amlodipine and may 
occur also with Twynsta:

Telmisartan
In patients taking telmisartan alone the following additional side effects have been reported:

Uncommon side effects (may affect up to 1 in 100 people): 
Urinary tract infections, upper respiratory tract infections (e.g. sore throat, inflamed sinuses, common 
cold), deficiency in red blood cells (anaemia), high potassium levels in the blood, shortness of breath, 
bloating, increased sweating, kidney damage including sudden inability of the kidneys to work, increased 
levels of creatinine.

Rare side effects (may affect up to 1 in 1,000 people):
Increase in certain white blood cells (eosinophilia), low platelet count (thrombocytopenia), allergic 
reaction (e.g. rash, itching, difficulty of breathing, wheezing, swelling of the face or low blood pressure),
low blood sugar levels (in diabetic patients), impaired vision, fast heart beat, upset stomach, abnormal 
liver function, hives (urticaria), medicine rash, inflammation of the tendons, flu-like illness (for example 
muscle pain, feeling generally unwell), decreased haemoglobin (a blood protein), increased levels of 
creatinine phosphokinase in the blood.

Most cases of abnormal liver function and liver disorder from post-marketing experience with telmisartan 
occurred in Japanese patients. Japanese patients are more likely to experience this side effect.

Amlodipine
In patients taking amlodipine alone the following additional side effects have been reported:

Common side effects (may affect up to 1 in 10 people):
Altered bowel habits, diarrhoea, constipation, visual disturbances, double vision, ankle swelling. 

Uncommon side effects (may affect up to 1 in 100 people):
Mood changes, impaired vision, ringing in the ears, shortness of breath, sneezing/running nose, hair loss, 
unusual bruising and bleeding (red blood cell damage), skin discolouration, increased sweating, difficulty 
passing urine, increased need to pass urine especially at night, enlarging of male breasts, pain, weight 
increased, weight decreased.

Rare side effects (may affect up to 1 in 1,000 people): 
Confusion.

Very rare side effects (may affect up to 1 in 10,000 people):
Reduced number of white blood cells (leucopenia), low platelet count (thrombocytopenia), allergic 
reaction (e.g. rash, itching, difficulty breathing, wheezing, swelling of the face or low blood pressure), 
excess sugar in blood , uncontrollable twitching or jerking movements, heart attack, irregular heart beat, 



129

inflammation of the blood vessels, inflamed pancreas, inflammation of the stomach lining (gastritis), 
inflammation of the liver, yellowing of the skin (jaundice), increased levels of hepatic enzymes with 
jaundice, rapid swelling of skin and mucosa (angioedema), severe skin reactions, hives (urticaria), severe 
allergic reactions with blistering eruptions of the skin and mucous membranes (exfoliative dermatitis, 
Stevens-Johnson-Syndrome), increased sensitivity of the skin to sun, increased muscle tension.

Not known (frequency cannot be estimated from the available data):
Severe allergic reactions with blistering eruptions of the skin and mucous membranes (toxic epidermal 
necrolysis).

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not 

listed in this leaflet. You can also report side effects directly via the national reporting system listed in 

Appendix V. By reporting side effects you can help provide more information on the safety of this 

medicine.

5. How to store Twynsta

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

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

This medicine does not require any special temperature storage conditions.Store in the original package 
in order to protect from light and moisture. Remove your Twynsta tablet from the blister only directly 
prior to intake.

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

6. Contents of the pack and other information

What Twynsta contains
 The active substances are telmisartan and amlodipine. 

Each tablet contains 40 mg telmisartan and 10 mg amlodipine (as amlodipine besilate).

 The other ingredients are colloidal anhydrous silica, brilliant blue FCF (E133), ferric oxide black 
(E172), ferric oxide yellow (E172), magnesium stearate, maize starch, meglumine, 
microcrystalline cellulose, povidone K25, pregelatinized starch prepared from maize starch, 
sodium hydroxide, sorbitol (E420).

What Twynsta looks like and contents of the pack
Twynsta 40 mg/10 mg tablets are blue and white oval shaped two layer tablets engraved with the product 
code A2 and the company logo on the white layer.

Twynsta is available in a folding box containing 14, 28, 56, 98 tablets in aluminium/aluminium blisters 
or containing 30 x 1, 90 x 1, 360 (4 x 90 x 1) tablets in aluminium/aluminium perforated unit dose 
blisters.

Not all pack sizes may be marketed.

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


130

Marketing Authorisation Holder Manufacturer
Boehringer Ingelheim International GmbH
Binger Str. 173
D-55216 Ingelheim am Rhein
Germany

Boehringer Ingelheim Pharma GmbH & Co. KG
Binger Str. 173
D-55216 Ingelheim am Rhein
Germany

Rottendorf Pharma GmbH
Ostenfelder Straße 51 - 61
D-59320 Ennigerloh
Germany



131

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

België/Belgique/Belgien
SCS Boehringer Ingelheim Comm.V
Tél/Tel: +32 2 773 33 11

Lietuva
Boehringer Ingelheim RCV GmbH & Co KG 
Lietuvos filialas
Tel.: +370 37 473922

България
Бьорингер Ингелхайм РЦВ ГмбХ и Ко КГ –
клон България
Тел: +359 2 958 79 98

Luxembourg/Luxemburg
SCS Boehringer Ingelheim Comm.V
Tél/Tel: +32 2 773 33 11

Česká republika
Boehringer Ingelheim spol. S r.o.
Tel: +420 234 655 111

Magyarország
Boehringer Ingelheim RCV GmbH & Co KG
Magyarországi Fióktelepe
Tel.: +36 1 299 89 00

Danmark
Boehringer Ingelheim Danmark A/S
Tlf: +45 39 15 88 88

Malta
Boehringer Ingelheim Ireland Ltd.
Tel: +353 1 295 9620

Deutschland
Boehringer Ingelheim Pharma GmbH & Co. KG
Tel: +49 (0) 800 77 90 900

Nederland
Boehringer Ingelheim b.v.
Tel: +31 (0) 800 22 55 889

Eesti
Boehringer Ingelheim RCV GmbH & Co KG
Eesti Filiaal
Tel: +372 612 8000

Norge
Boehringer Ingelheim Norway KS
Tlf: +47 66 76 13 00

Ελλάδα
Boehringer Ingelheim Ellas A.E.
Tηλ: +30 2 10 89 06 300

Österreich
Boehringer Ingelheim RCV GmbH & Co KG
Tel: +43 1 80 105-7870

España
Boehringer Ingelheim España, S.A.
Tel: +34 93 404 51 00

Polska
Boehringer Ingelheim Sp.zo.o.
Tel.: +48 22 699 0 699

France
Boehringer Ingelheim France S.A.S.
Tél: +33 3 26 50 45 33

Portugal
Boehringer Ingelheim, Unipessoal, Lda.
Tel: +351 21 313 53 00

Hrvatska
Boehringer Ingelheim Zagreb d.o.o.
Tel: +385 1 2444 600

România
Boehringer Ingelheim RCV GmbH & Co KG
Viena - Sucursala Bucuresti
Tel: +40 21 302 2800

Ireland
Boehringer Ingelheim Ireland Ltd.
Tel: +353 1 295 9620

Slovenija
Boehringer Ingelheim RCV GmbH & Co KG
Podružnica Ljubljana
Tel: +386 1 586 40 00



132

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Boehringer Ingelheim RCV GmbH & Co KG
organizačná zložka
Tel: +421 2 5810 1211

Italia
Boehringer Ingelheim Italia S.p.A.
Tel: +39 02 5355 1

Suomi/Finland
Boehringer Ingelheim Finland Ky
Puh/Tel: +358 10 3102 800

Κύπρος
Boehringer Ingelheim Ellas A.E.
Tηλ: +30 2 10 89 06 300

Sverige
Boehringer Ingelheim AB
Tel: +46 8 721 21 00

Latvija
Boehringer Ingelheim RCV GmbH & Co KG
Latvijas filiāle
Tel: +371 67 240 011

United Kingdom
Boehringer Ingelheim Ltd.
Tel: +44 1344 424 600

This leaflet was last revised in 

Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu/.

http://www.emea.europa.eu


133

Package leaflet: Information for the user
Twynsta 80 mg/5 mg tablets

Telmisartan/Amlodipine

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

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

effects not listed in this leaflet. See section 4.

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

1. What Twynsta is and what it is used for

Twynsta tablets contain two active substances called telmisartan and amlodipine. Both of these 
substances help to control your high blood pressure:
 Telmisartan belongs to a group of substances called “angiotensin-II receptor antagonists”. 

Angiotensin II is a substance produced in the body which causes blood vessels to narrow, thus 
increasing blood pressure. Telmisartan works by blocking the effect of angiotensin II.

 Amlodipine belongs to a group of substances called “calcium channel blockers”. Amlodipine stops 
calcium from moving into the blood vessel wall which stops the blood vessels from tightening.

This means that both of these active substances work together to help stop your blood vessels tightening. 
As a result, the blood vessels relax and blood pressure is lowered.

Twynsta is used to treat high blood pressure
 in adult patients whose blood pressure is not controlled enough with amlodipine alone.
 in adult patients who already receive telmisartan and amlodipine from separate tablets and who 

wish to take instead the same doses in one tablet for convenience.

High blood pressure, if not treated, can damage blood vessels in several organs, which puts patients at 
risk of serious events such as heart attack, heart or kidney failure, stroke, or blindness. There are usually 
no symptoms of high blood pressure before damage occurs. Thus it is important to regularly measure 
blood pressure to verify if it is within the normal range.

2. What you need to know before you take Twynsta

Do not take Twynsta
 if you are allergic to telmisartan or amlodipine or any of the other ingredients of this medicine 

(listed in section 6).
 if you are allergic to other medicines of the dihydropyridine type (one type of calcium channel 

blocker).
 if you are more than 3 months pregnant. (It is also better to avoid Twynsta in early pregnancy – see 

Pregnancy section.)



134

 if you have severe liver problems or biliary obstruction (problems with drainage of the bile from 
the liver and gall bladder).

 if you have narrowing of the aortic heart valve (aortic stenosis) or cardiogenic shock (a condition 
where your heart is unable to supply enough blood to the body). 

 if you suffer from heart failure after a heart attack.
 if you have diabetes or impaired kidney function and you are treated with a blood pressure 

lowering medicine containing aliskiren.

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

Warnings and precautions
Talk to your doctor before taking Twynsta if you are suffering or have ever suffered from any of the 
following conditions or illnesses:
 Kidney disease or kidney transplant.
 Narrowing of the blood vessels to one or both kidneys (renal artery stenosis).
 Liver disease.
 Heart trouble.
 Raised aldosterone levels (which lead to 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.
 Narrowing of the aorta (aortic stenosis).
 Heart-associated chest pain also at rest or with minimal effort (unstable angina pectoris).
 A heart attack within the last four weeks.

Talk to your doctor before taking Twynsta:
 if you are taking any of the following medicines used to treat high blood pressure:

- an ACE-inhibitor (for example enalapril, lisinopril, ramipril), in particular if you have diabetes-
related kidney problems.
- aliskiren.
Your doctor may check your kidney function, blood pressure, and the amount of electrolytes (e.g. 
potassium) in your blood at regular intervals. See also “Do not take Twynsta”.

 if you are elderly and your dose needs to be increased.

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

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

Other medicines and Twynsta
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. 
Your doctor may need to change the dose of these other medicines or take other precautions. In some 
cases you may have to stop taking one of the medicines. This applies especially to the medicines listed 
below:
 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’).
 Angiotensin II receptor antagonists.
 ACE-inhibitors or aliskiren (see also information under the headings “Do not take Twynsta” and 

“Warnings and precautions”).



135

 NSAIDs (non steroidal anti-inflammatory medicines, e.g. acetylsalicylic acid or ibuprofen), 
heparin, immunosuppressives (e.g. cyclosporin or tacrolimus), and the antibiotic trimethoprim.

 Rifampicin, erythromycin, clarithromycin (antibiotics)
 St. John’s wort.
 Dantrolene (infusion for severe body temperature abnormalities).
 Medicines used to alter the way your immune system works (e.g. sirolimus, temsirolimus and 

everolimus).
 Medicines used for HIV/AIDS (e.g. ritonavir) or for treatment of fungal infections (e.g. 

ketoconazole).
 Diltiazem (cardiac medicine).
 Simvastatin to treat elevated levels of cholesterol.
 Digoxin.

As with other blood pressure lowering medicines, the effect of Twynsta may be reduced when you take 
NSAIDs (non steroidal anti-inflammatory medicines, e.g. acetylsalicylic acid or ibuprofen) or 
corticosteroids.

Twynsta may increase the blood pressure lowering effect of other medicines used to treat high blood 
pressure or of medicines with blood pressure lowering potential (e.g. baclofen, amifostine, neuroleptics 
or antidepressants).

Twynsta with food and drink
Low blood pressure may be aggravated by alcohol. You may notice this as dizziness when standing up.

Grapefruit juice and grapefruit should not be consumed when you take Twynsta. This is because 
grapefruit and grapefruit juice may lead to increased blood levels of the active ingredient amlodipine in 
some patients and may increase the blood pressure lowering effect of Twynsta.

Pregnancy and breast-feeding
Pregnancy
You must tell your doctor if you think you might be pregnant or are planning to have a baby. Your doctor 
will normally advise you to stop taking Twynsta before you become pregnant or as soon as you know you 
are pregnant and will advise you to take another medicine instead of Twynsta. Twynsta 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
Amlodipine has been shown to pass into breast milk in small amounts.
Tell your doctor if you are breast-feeding or about to start breast-feeding. Twynsta 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.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines
Some people may experience side effects such as fainting, sleepiness, dizziness or a feeling of spinning 
(vertigo) when they are treated for high blood pressure. If you experience these side effects, do not drive 
or use machines.

Twynsta contains sorbitol 
This medicine contains 337.28 mg sorbitol in each tablet.

Sorbitol is a source of fructose. If your doctor has told you that you have an intolerance to some sugars or 
if you have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which a 
person cannot break down fructose, talk to your doctor before you take or receive this medicine.



136

Twynsta contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-
free’.

3. How to take Twynsta

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

The recommended dose is one tablet a day. Try to take the tablet at the same time each day.
Remove your Twynsta tablet from the blister only directly prior to intake.

You can take Twynsta with or without food. The tablets should be swallowed with some water or other 
non-alcoholic drink.

If your liver is not working properly, the usual dose should not exceed one 40 mg/5 mg tablet or 
one 40 mg/10 mg tablet per day.

If you take more Twynsta than you should
If you accidentally take too many tablets, contact your doctor, pharmacist, or your nearest hospital 
emergency department immediately. You might experience low blood pressure and rapid heart beat. Slow 
heart beat, dizziness, reduced kidney function including kidney failure, marked and prolonged low blood 
pressure including shock and death have also been reported.

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

If you stop taking Twynsta
It is important that you take Twynsta every day until your doctor tells you otherwise. If you have the 
impression that the effect of Twynsta 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, this medicine can cause side effects, although not everybody gets them. 

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

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

Sepsis (often called "blood poisoning", is a severe infection of the whole-body with high fever and the 
feeling of being severely ill), rapid swelling of the skin and mucosa (angioedema); these side effects are 
rare (may affect up to 1 in 1,000 people) but are extremely serious and patients should stop taking the 
medicine and see their doctor immediately. If these effects are not treated they could be fatal. Increased 
incidence of sepsis has been observed with telmisartan only, however can not be ruled out for Twynsta.

Common side effects (may affect up to 1 in 10 people): 
Dizziness, ankle swelling (oedema).



137

Uncommon side effects (may affect up to 1 in 100 people): 
Sleepiness, migraine, headache, tingling or numbness of the hands or feet, feeling of spinning (vertigo), 
slow heart rate, palpitations (awareness of your heart beat), low blood pressure (hypotension), dizziness 
on standing up (orthostatic hypotension), flushing, cough, stomach ache (abdominal pain), diarrhoea, 
feeling sick (nausea), itching, joint pain, muscle cramps, muscle pain, inability to obtain an erection, 
weakness, chest pain, tiredness, swelling (oedema), increased levels of hepatic enzymes.

Rare side effects (may affect up to 1 in 1,000 people): 
Urinary bladder infection, feeling sad (depression), feeling anxious, sleeplessness, fainting, nerve 
damage in the hands or feet, reduced sense of touch, taste abnormalities, trembling, vomiting, enlarged 
gums, discomfort in the abdomen, dry mouth, eczema (a skin disorder), redness of skin, rash, back pain, 
leg pain, urge to urinate during the night, feeling unwell (malaise), increased levels of uric acid in the 
blood.

Very rare side effect (may affect up to 1 in 10,000 people):
Progressive scarring of lung tissue (interstitial lung disease [mainly pneumonia of the interstitium and 
pneumonia with excess eosinophils])
The following side effects have been observed with the components telmisartan or amlodipine and may 
occur also with Twynsta:

Telmisartan
In patients taking telmisartan alone the following additional side effects have been reported:

Uncommon side effects (may affect up to 1 in 100 people): 
Urinary tract infections, upper respiratory tract infections (e.g. sore throat, inflamed sinuses, common 
cold), deficiency in red blood cells (anaemia), high potassium levels in the blood, shortness of breath, 
bloating, increased sweating, kidney damage including sudden inability of the kidneys to work, increased 
levels of creatinine.

Rare side effects (may affect up to 1 in 1,000 people):
Increase in certain white blood cells (eosinophilia), low platelet count (thrombocytopenia), allergic 
reaction (e.g. rash, itching, difficulty of breathing, wheezing, swelling of the face or low blood pressure),
low blood sugar levels (in diabetic patients), impaired vision, fast heart beat, upset stomach, abnormal 
liver function, hives (urticaria), medicine rash, inflammation of the tendons, flu-like illness (for example 
muscle pain, feeling generally unwell), decreased haemoglobin (a blood protein), increased levels of 
creatinine phosphokinase in the blood.

Most cases of abnormal liver function and liver disorder from post-marketing experience with telmisartan 
occurred in Japanese patients. Japanese patients are more likely to experience this side effect.

Amlodipine
In patients taking amlodipine alone the following additional side effects have been reported:

Common side effects (may affect up to 1 in 10 people):
Altered bowel habits, diarrhoea, constipation, visual disturbances, double vision, ankle swelling. 

Uncommon side effects (may affect up to 1 in 100 people):
Mood changes, impaired vision, ringing in the ears, shortness of breath, sneezing/running nose, hair loss, 
unusual bruising and bleeding (red blood cell damage), skin discolouration, increased sweating, difficulty 
passing urine, increased need to pass urine especially at night, enlarging of male breasts, pain, weight 
increased, weight decreased.

Rare side effects (may affect up to 1 in 1,000 people): 
Confusion.



138

Very rare side effects (may affect up to 1 in 10,000 people):
Reduced number of white blood cells (leucopenia), low platelet count (thrombocytopenia), allergic 
reaction (e.g. rash, itching, difficulty breathing, wheezing, swelling of the face or low blood pressure), 
excess sugar in blood , uncontrollable twitching or jerking movements, heart attack, irregular heart beat, 
inflammation of the blood vessels, inflamed pancreas, inflammation of the stomach lining (gastritis), 
inflammation of the liver, yellowing of the skin (jaundice), increased levels of hepatic enzymes with 
jaundice, rapid swelling of skin and mucosa (angioedema), severe skin reactions, hives (urticaria), severe 
allergic reactions with blistering eruptions of the skin and mucous membranes (exfoliative dermatitis, 
Stevens-Johnson-Syndrome), increased sensitivity of the skin to sun, increased muscle tension.

Not known (frequency cannot be estimated from the available data):
Severe allergic reactions with blistering eruptions of the skin and mucous membranes (toxic epidermal 
necrolysis).

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not 

listed in this leaflet. You can also report side effects directly via the national reporting system listed in 

Appendix V. By reporting side effects you can help provide more information on the safety of this 

medicine.

5. How to store Twynsta

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

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

This medicine does not require any special temperature storage conditions. Store in the original package 
in order to protect from light and moisture. Remove your Twynsta tablet from the blister only directly 
prior to intake.

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

6. Contents of the pack and other information

What Twynsta contains
 The active substances are telmisartan and amlodipine. 

Each tablet contains 80 mg telmisartan and 5 mg amlodipine (as amlodipine besilate).

 The other ingredients are colloidal anhydrous silica, brilliant blue FCF (E133), ferric oxide black 
(E172), ferric oxide yellow (E172), magnesium stearate, maize starch, meglumine, 
microcrystalline cellulose, povidone K25, pregelatinized starch prepared from maize starch, 
sodium hydroxide, sorbitol (E420).

What Twynsta looks like and contents of the pack
Twynsta 80 mg/5 mg tablets are blue and white oval shaped two layer tablets engraved with the product 
code A3 and the company logo on the white layer.

Twynsta is available in a folding box containing 14, 28, 56, 98 tablets in aluminium/aluminium blisters 
or containing 30 x 1, 90 x 1, 360 (4 x 90 x 1) tablets in aluminium/aluminium perforated unit dose 
blisters.

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


139

Not all pack sizes may be marketed.

Marketing Authorisation Holder Manufacturer
Boehringer Ingelheim International GmbH
Binger Str. 173
D-55216 Ingelheim am Rhein
Germany

Boehringer Ingelheim Pharma GmbH & Co. KG
Binger Str. 173
D-55216 Ingelheim am Rhein
Germany

Rottendorf Pharma GmbH
Ostenfelder Straße 51 - 61
D-59320 Ennigerloh
Germany



140

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

België/Belgique/Belgien
SCS Boehringer Ingelheim Comm.V
Tél/Tel: +32 2 773 33 11

Lietuva
Boehringer Ingelheim RCV GmbH & Co KG 
Lietuvos filialas
Tel.: +370 37 473922

България
Бьорингер Ингелхайм РЦВ ГмбХ и Ко КГ -
клон България
Тел: +359 2 958 79 98

Luxembourg/Luxemburg
SCS Boehringer Ingelheim Comm.V
Tél/Tel: +32 2 773 33 11

Česká republika
Boehringer Ingelheim spol. s r.o.
Tel: +420 234 655 111

Magyarország
Boehringer Ingelheim RCV GmbH & Co KG
Magyarországi Fióktelepe
Tel.: +36 1 299 89 00

Danmark
Boehringer Ingelheim Danmark A/S
Tlf: +45 39 15 88 88

Malta
Boehringer Ingelheim Ireland Ltd.
Tel: +353 1 295 9620

Deutschland
Boehringer Ingelheim Pharma GmbH & Co. KG
Tel: +49 (0) 800 77 90 900

Nederland
Boehringer Ingelheim b.v.
Tel: +31 (0) 800 22 55 889

Eesti
Boehringer Ingelheim RCV GmbH & Co KG
Eesti Filiaal
Tel: +372 612 8000

Norge
Boehringer Ingelheim Norway KS
Tlf: +47 66 76 13 00

Ελλάδα
Boehringer Ingelheim Ellas A.E.
Tηλ: +30 2 10 89 06 300

Österreich
Boehringer Ingelheim RCV GmbH & Co KG
Tel: +43 1 80 105-7870

España
Boehringer Ingelheim España, S.A.
Tel: +34 93 404 51 00

Polska
Boehringer Ingelheim Sp.zo.o.
Tel.: +48 22 699 0 699

France
Boehringer Ingelheim France S.A.S.
Tél: +33 3 26 50 45 33

Portugal
Boehringer Ingelheim, Unipessoal, Lda.
Tel: +351 21 313 53 00

Hrvatska
Boehringer Ingelheim Zagreb d.o.o.
Tel: +385 1 2444 600

România
Boehringer Ingelheim RCV GmbH & Co KG
Viena - Sucursala Bucuresti
Tel: +40 21 302 2800

Ireland
Boehringer Ingelheim Ireland Ltd.
Tel: +353 1 295 9620

Slovenija
Boehringer Ingelheim RCV GmbH & Co KG
Podružnica Ljubljana
Tel: +386 1 586 40 00



141

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Boehringer Ingelheim RCV GmbH & Co KG
organizačná zložka
Tel: +421 2 5810 1211

Italia
Boehringer Ingelheim Italia S.p.A.
Tel: +39 02 5355 1

Suomi/Finland
Boehringer Ingelheim Finland Ky
Puh/Tel: +358 10 3102 800

Κύπρος
Boehringer Ingelheim Ellas A.E.
Tηλ: +30 2 10 89 06 300

Sverige
Boehringer Ingelheim AB
Tel: +46 8 721 21 00

Latvija
Boehringer Ingelheim RCV GmbH & Co KG
Latvijas filiāle
Tel: +371 67 240 011

United Kingdom
Boehringer Ingelheim Ltd.
Tel: +44 1344 424 600

This leaflet was last revised in 

Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/.

http://www.emea.europa.eu


142

Package leaflet: Information for the user
Twynsta 80 mg/10 mg tablets

Telmisartan/Amlodipine

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

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

effects not listed in this leaflet. See section 4.

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

1. What Twynsta is and what it is used for

Twynsta tablets contain two active substances called telmisartan and amlodipine. Both of these 
substances help to control your high blood pressure:
 Telmisartan belongs to a group of substances called “angiotensin-II receptor antagonists”. 

Angiotensin II is a substance produced in the body which causes blood vessels to narrow, thus 
increasing blood pressure. Telmisartan works by blocking the effect of angiotensin II.

 Amlodipine belongs to a group of substances called “calcium channel blockers”. Amlodipine stops 
calcium from moving into the blood vessel wall which stops the blood vessels from tightening.

This means that both of these active substances work together to help stop your blood vessels tightening. 
As a result, the blood vessels relax and blood pressure is lowered.

Twynsta is used to treat high blood pressure
 in adult patients whose blood pressure is not controlled enough with amlodipine alone.
 in adult patients who already receive telmisartan and amlodipine from separate tablets and who 

wish to take instead the same doses in one tablet for convenience.

High blood pressure, if not treated, can damage blood vessels in several organs, which puts patients at 
risk of serious events such as heart attack, heart or kidney failure, stroke, or blindness. There are usually 
no symptoms of high blood pressure before damage occurs. Thus it is important to regularly measure 
blood pressure to verify if it is within the normal range.

2. What you need to know before you take Twynsta

Do not take Twynsta
 if you are allergic to telmisartan or amlodipine or any of the other ingredients of this medicine 

(listed in section 6).
 if you are allergic to other medicines of the dihydropyridine type (one type of calcium channel 

blocker).
 if you are more than 3 months pregnant. (It is also better to avoid Twynsta in early pregnancy – see 

Pregnancy section.)



143

 if you have severe liver problems or biliary obstruction (problems with drainage of the bile from 
the liver and gall bladder).

 if you have narrowing of the aortic heart valve (aortic stenosis) or cardiogenic shock (a condition 
where your heart is unable to supply enough blood to the body). 

 if you suffer from heart failure after a heart attack.
 if you have diabetes or impaired kidney function and you are treated with a blood pressure 

lowering medicine containing aliskiren.

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

Warnings and precautions
Talk to your doctor before taking Twynsta if you are suffering or have ever suffered from any of the 
following conditions or illnesses:
 Kidney disease or kidney transplant.
 Narrowing of the blood vessels to one or both kidneys (renal artery stenosis).
 Liver disease.
 Heart trouble.
 Raised aldosterone levels (which lead to 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.
 Narrowing of the aorta (aortic stenosis).
 Heart-associated chest pain also at rest or with minimal effort (unstable angina pectoris).
 A heart attack within the last four weeks.

Talk to your doctor before taking Twynsta:
 if you are taking any of the following medicines used to treat high blood pressure:

- an ACE-inhibitor (for example enalapril, lisinopril, ramipril), in particular if you have diabetes-
related kidney problems.
- aliskiren.
Your doctor may check your kidney function, blood pressure, and the amount of electrolytes (e.g. 
potassium) in your blood at regular intervals. See also “Do not take Twynsta”.

 if you are elderly and your dose needs to be increased.

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

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

Other medicines and Twynsta
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. 
Your doctor may need to change the dose of these other medicines or take other precautions. In some 
cases you may have to stop taking one of the medicines. This applies especially to the medicines listed 
below:
 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’).
 Angiotensin II receptor antagonists.
 ACE-inhibitors or aliskiren (see also information under the headings “Do not take Twynsta” and 

“Warnings and precautions”).



144

 NSAIDs (non steroidal anti-inflammatory medicines, e.g. acetylsalicylic acid or ibuprofen), 
heparin, immunosuppressives (e.g. cyclosporin or tacrolimus), and the antibiotic trimethoprim.

 Rifampicin, erythromycin, clarithromycin (antibiotics).
 St. John’s wort.
 Dantrolene (infusion for severe body temperature abnormalities).
 Medicines used to alter the way your immune system works (e.g. sirolimus, temsirolimus and 

everolimus).
 Medicines used for HIV/AIDS (e.g. ritonavir) or for treatment of fungal infections (e.g. 

ketoconazole).
 Diltiazem (cardiac medicine).
 Simvastatin to treat elevated levels of cholesterol.
 Digoxin.

As with other blood pressure lowering medicines, the effect of Twynsta may be reduced when you take 
NSAIDs (non steroidal anti-inflammatory medicines, e.g. acetylsalicylic acid or ibuprofen) or 
corticosteroids.

Twynsta may increase the blood pressure lowering effect of other medicines used to treat high blood 
pressure or of medicines with blood pressure lowering potential (e.g. baclofen, amifostine, neuroleptics 
or antidepressants).

Twynsta with food and drink
Low blood pressure may be aggravated by alcohol. You may notice this as dizziness when standing up.

Grapefruit juice and grapefruit should not be consumed when you take Twynsta. This is because 
grapefruit and grapefruit juice may lead to increased blood levels of the active ingredient amlodipine in 
some patients and may increase the blood pressure lowering effect of Twynsta.

Pregnancy and breast-feeding
Pregnancy
You must tell your doctor if you think you might be pregnant or are planning to have a baby. Your doctor 
will normally advise you to stop taking Twynsta before you become pregnant or as soon as you know you 
are pregnant and will advise you to take another medicine instead of Twynsta. Twynsta 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
Amlodipine has been shown to pass into breast milk in small amounts.
Tell your doctor if you are breast-feeding or about to start breast-feeding. Twynsta 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.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines
Some people may experience side effects such as fainting, sleepiness, dizziness or a feeling of spinning 
(vertigo) when they are treated for high blood pressure. If you experience these side effects, do not drive 
or use machines.

Twynsta contains sorbitol 
This medicine contains 337.28 mg sorbitol in each tablet.

Sorbitol is a source of fructose. If your doctor has told you that you have an intolerance to some sugars or 
if you have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which a 
person cannot break down fructose, talk to your doctor before you take or receive this medicine.



145

Twynsta contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-
free’.

3. How to take Twynsta

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

The recommended dose is one tablet a day. Try to take the tablet at the same time each day.
Remove your Twynsta tablet from the blister only directly prior to intake.

You can take Twynsta with or without food. The tablets should be swallowed with some water or other 
non-alcoholic drink.

If your liver is not working properly, the usual dose should not exceed one 40 mg/5 mg tablet or 
one 40 mg/10 mg tablet per day.

If you take more Twynsta than you should
If you accidentally take too many tablets, contact your doctor, pharmacist, or your nearest hospital 
emergency department immediately. You might experience low blood pressure and rapid heart beat. Slow 
heart beat, dizziness, reduced kidney function including kidney failure, marked and prolonged low blood 
pressure including shock and death have also been reported.

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

If you stop taking Twynsta
It is important that you take Twynsta every day until your doctor tells you otherwise. If you have the 
impression that the effect of Twynsta 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, this medicine can cause side effects, although not everybody gets them. 

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

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

Sepsis (often called "blood poisoning", is a severe infection of the whole-body with high fever and the 
feeling of being severely ill), rapid swelling of the skin and mucosa (angioedema); these side effects are 
rare (may affect up to 1 in 1,000 people) but are extremely serious and patients should stop taking the 
medicine and see their doctor immediately. If these effects are not treated they could be fatal. Increased 
incidence of sepsis has been observed with telmisartan only, however can not be ruled out for Twynsta.

Common side effects (may affect up to 1 in 10 people):
Dizziness, ankle swelling (oedema).



146

Uncommon side effects (may affect up to 1 in 100 people):
Sleepiness, migraine, headache, tingling or numbness of the hands or feet, feeling of spinning (vertigo), 
slow heart rate, palpitations (awareness of your heart beat), low blood pressure (hypotension), dizziness 
on standing up (orthostatic hypotension), flushing, cough, stomach ache (abdominal pain), diarrhoea, 
feeling sick (nausea), itching, joint pain, muscle cramps, muscle pain, inability to obtain an erection, 
weakness, chest pain, tiredness, swelling (oedema), increased levels of hepatic enzymes.

Rare side effects (may affect up to 1 in 1,000 people):
Urinary bladder infection, feeling sad (depression), feeling anxious, sleeplessness, fainting, nerve 
damage in the hands or feet, reduced sense of touch, taste abnormalities, trembling, vomiting, enlarged 
gums, discomfort in the abdomen, dry mouth, eczema (a skin disorder), redness of skin, rash, back pain, 
leg pain, urge to urinate during the night, feeling unwell (malaise), increased levels of uric acid in the 
blood.

Very rare side effect (may affect up to 1 in 10,000 people):
Progressive scarring of lung tissue (interstitial lung disease [mainly pneumonia of the interstitium and 
pneumonia with excess eosinophils])

The following side effects have been observed with the components telmisartan or amlodipine and may 
occur also with Twynsta:

Telmisartan
In patients taking telmisartan alone the following additional side effects have been reported:

Uncommon side effects (may affect up to 1 in 100 people):
Urinary tract infections, upper respiratory tract infections (e.g. sore throat, inflamed sinuses, common 
cold), deficiency in red blood cells (anaemia), high potassium levels in the blood, shortness of breath, 
bloating, increased sweating, kidney damage including sudden inability of the kidneys to work, increased 
levels of creatinine.

Rare side effects (may affect up to 1 in 1,000 people): 
Increase in certain white blood cells (eosinophilia), low platelet count (thrombocytopenia), allergic 
reaction (e.g. rash, itching, difficulty of breathing, wheezing, swelling of the face or low blood pressure),
low blood sugar levels (in diabetic patients), impaired vision, fast heart beat, upset stomach, abnormal 
liver function, hives (urticaria), medicine rash, inflammation of the tendons, flu-like illness (for example 
muscle pain, feeling generally unwell), decreased haemoglobin (a blood protein), increased levels of 
creatinine phosphokinase in the blood.

Most cases of abnormal liver function and liver disorder from post-marketing experience with telmisartan 
occurred in Japanese patients. Japanese patients are more likely to experience this side effect.

Amlodipine
In patients taking amlodipine alone the following additional side effects have been reported:

Common side effects (may affect up to 1 in 10 people):
Altered bowel habits, diarrhoea, constipation, visual disturbances, double vision, ankle swelling. 

Uncommon side effects (may affect up to 1 in 100 people):
Mood changes, impaired vision, ringing in the ears, shortness of breath, sneezing/running nose, hair loss, 
unusual bruising and bleeding (red blood cell damage), skin discolouration, increased sweating, difficulty 
passing urine, increased need to pass urine especially at night, enlarging of male breasts, pain, weight 
increased, weight decreased.

Rare side effects (may affect up to 1 in 1,000 people): 
Confusion.



147

Very rare side effects (may affect up to 1 in 10,000 people):
Reduced number of white blood cells (leucopenia), low platelet count (thrombocytopenia), allergic 
reaction (e.g. rash, itching, difficulty breathing, wheezing, swelling of the face or low blood pressure), 
excess sugar in blood , uncontrollable twitching or jerking movements, heart attack, irregular heart beat, 
inflammation of the blood vessels, inflamed pancreas, inflammation of the stomach lining (gastritis), 
inflammation of the liver, yellowing of the skin (jaundice), increased levels of hepatic enzymes with 
jaundice, rapid swelling of skin and mucosa (angioedema), severe skin reactions, hives (urticaria), severe 
allergic reactions with blistering eruptions of the skin and mucous membranes (exfoliative dermatitis, 
Stevens-Johnson-Syndrome), increased sensitivity of the skin to sun, increased muscle tension.

Not known (frequency cannot be estimated from the available data):
Severe allergic reactions with blistering eruptions of the skin and mucous membranes (toxic epidermal 
necrolysis).

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not 

listed in this leaflet. You can also report side effects directly via the national reporting system listed in 

Appendix V. By reporting side effects you can help provide more information on the safety of this 

medicine.

5. How to store Twynsta

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

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

This medicine does not require any special temperature storage conditions. Store in the original package 
in order to protect from light and moisture. Remove your Twynsta tablet from the blister only directly 
prior to intake.

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

6. Contents of the pack and other information

What Twynsta contains
 The active substances are telmisartan and amlodipine. 

Each tablet contains 80 mg telmisartan and 10 mg amlodipine (as amlodipine besilate).

 The other ingredients are colloidal anhydrous silica, brilliant blue FCF (E133), ferric oxide black 
(E172), ferric oxide yellow (E172), magnesium stearate, maize starch, meglumine, 
microcrystalline cellulose, povidone K25, pregelatinized starch prepared from maize starch, 
sodium hydroxide, sorbitol (E420).

What Twynsta looks like and contents of the pack
Twynsta 80 mg/10 mg tablets are blue and white oval shaped two layer tablets engraved with the product 
code A4 and the company logo on the white layer.

Twynsta is available in a folding box containing 14, 28, 56, 98 tablets in aluminium/aluminium blisters 
or containing 30 x 1, 90 x 1, 360 (4 x 90 x 1) tablets in aluminium/aluminium perforated unit dose 
blisters.

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


148

Not all pack sizes may be marketed.

Marketing Authorisation Holder Manufacturer
Boehringer Ingelheim International GmbH
Binger Str. 173
D-55216 Ingelheim am Rhein
Germany

Boehringer Ingelheim Pharma GmbH & Co. KG
Binger Str. 173
D-55216 Ingelheim am Rhein
Germany

Rottendorf Pharma GmbH
Ostenfelder Straße 51 - 61
D-59320 Ennigerloh
Germany



149

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

België/Belgique/Belgien
SCS Boehringer Ingelheim Comm.V
Tél/Tel: +32 2 773 33 11

Lietuva
Boehringer Ingelheim RCV GmbH & Co KG 
Lietuvos filialas
Tel.: +370 37 473922

България
Бьорингер Ингелхайм РЦВ ГмбХ и Ко КГ -
клон България
Тел: +359 2 958 79 98

Luxembourg/Luxemburg
SCS Boehringer Ingelheim Comm.V
Tél/Tel: +32 2 773 33 11

Česká republika
Boehringer Ingelheim spol. s r.o.
Tel: +420 234 655 111

Magyarország
Boehringer Ingelheim RCV GmbH & Co KG
Magyarországi Fióktelepe
Tel.: +36 1 299 89 00

Danmark
Boehringer Ingelheim Danmark A/S
Tlf: +45 39 15 88 88

Malta
Boehringer Ingelheim Ireland Ltd.
Tel: +353 1 295 9620

Deutschland
Boehringer Ingelheim Pharma GmbH & Co. KG
Tel: +49 (0) 800 77 90 900

Nederland
Boehringer Ingelheim b.v.
Tel: +31 (0) 800 22 55 889

Eesti
Boehringer Ingelheim RCV GmbH & Co KG
Eesti Filiaal
Tel: +372 612 8000

Norge
Boehringer Ingelheim Norway KS
Tlf: +47 66 76 13 00

Ελλάδα
Boehringer Ingelheim Ellas A.E.
Tηλ: +30 2 10 89 06 300

Österreich
Boehringer Ingelheim RCV GmbH & Co KG
Tel: +43 1 80 105-7870

España
Boehringer Ingelheim España, S.A.
Tel: +34 93 404 51 00

Polska
Boehringer Ingelheim Sp.zo.o.
Tel.: +48 22 699 0 699

France
Boehringer Ingelheim France S.A.S.
Tél: +33 3 26 50 45 33

Portugal
Boehringer Ingelheim, Unipessoal, Lda.
Tel: +351 21 313 53 00

Hrvatska
Boehringer Ingelheim Zagreb d.o.o.
Tel: +385 1 2444 600

România
Boehringer Ingelheim RCV GmbH & Co KG
Viena - Sucursala Bucuresti
Tel: +40 21 302 2800

Ireland
Boehringer Ingelheim Ireland Ltd.
Tel: +353 1 295 9620

Slovenija
Boehringer Ingelheim RCV GmbH & Co KG
Podružnica Ljubljana
Tel: +386 1 586 40 00



150

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Boehringer Ingelheim RCV GmbH & Co KG
organizačná zložka
Tel: +421 2 5810 1211

Italia
Boehringer Ingelheim Italia S.p.A.
Tel: +39 02 5355 1

Suomi/Finland
Boehringer Ingelheim Finland Ky
Puh/Tel: +358 10 3102 800

Κύπρος
Boehringer Ingelheim Ellas A.E.
Tηλ: +30 2 10 89 06 300

Sverige
Boehringer Ingelheim AB
Tel: +46 8 721 21 00

Latvija
Boehringer Ingelheim RCV GmbH & Co KG
Latvijas filiāle
Tel: +371 67 240 011

United Kingdom
Boehringer Ingelheim Ltd.
Tel: +44 1344 424 600

This leaflet was last revised in 

Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/.

http://www.emea.europa.eu

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