Trade name
of Tvinsta®
the International unlicensed name
Is not present
the Dosage form
of the Tablet of 80 mg / 5 mg, 80 mg / 10 mg
Structure
One tablet contains
a layer of a telmisartan
active agent - telmisartan 80 mg,
excipients: sodium hydroxide, K25 povidone, meglumin, sorbitol, magnesium stearate
a layer of an amlodipin
active agent - an amlodipina besilat 6.935 mg or 13.870 mg (it is equivalent an amlodipina of 5 mg or 10 mg respectively)
excipients: microcrystalline cellulose, starch prezhelatinizirovanny, starch corn, silicon dioxide colloidal, mix of dyes, magnesium stearate.
Description
of the Tablet of an oval form, biconvex, two-layer: one layer from white till almost white color, other layer of blue color. On a white surface of tablets there is a logo of firm and an engraving of A3 (for a dosage of 80 mg / 5 mg), other party of a tablet smooth.
Tablets of an oval form, biconvex, two-layer: one layer from white till almost white color, other layer of blue color. On a white surface of tablets there is a logo of firm and an engraving of A4 (for a dosage of 80 mg / 10 mg), other party of a tablet smooth.
Pharmacological group
of Angiotensin II antagonists in a combination with other drugs.
Antagonists of angiotensin II and blockers of calcium channels.
Telmisartan and amlodipin.
ATH C09DB04 code
the Pharmacological
Pharmacokinetics Pharmacokinetics properties of a combination of the fixed doses
the Speed and extent of absorption of drug TVINSTA are equivalent to bioavailability of a telmisartan and an amlodipin in case of their separate use.
Pharmacokinetics of the separate
Absorption components. Absorption of a telmisartan happens quickly though amounts of the absorbed drug are various. The average absolute bioavailability of a telmisartan is about 50%. Meal slightly reduces bioavailability of a telmisartan with reduction of value of the area under a curve concentration in plasma time (AUC), varies from 6% at reception in a dose 40 mg up to 19% at reception in a dose of 160 mg. In 3 h after reception of a telmisartan its concentration in blood plasma is identical to all doses, regardless of meal. Insignificant reduction of AUC does not cause decrease in therapeutic effectiveness.
After reception of one amlodipin inside in therapeutic doses the maximum concentration in plasma is reached in 6-12 hours. The calculated absolute bioavailability is from 64% to 80%. Meal does not influence bioavailability of an amlodipin.
Distribution. Telmisartan possesses high extent of linking with proteins of plasma (& gt, 99.5%), generally with albumine and alfa-1 an acid glycoprotein. The average constant visible volume of distribution of Vss is about 500 l that indicates additional linking with fabrics.
The volume of distribution of an amlodipin is about 21 l/kg.
In the researches in vitro it is shown that at patients about 97.5% of the circulating amlodipin are connected with hypertensia with proteins of plasma.
Metabolism. Telmisartan is metabolized by conjugation with a glucuronide. The pharmacological activity of a conjugate is not found.
Amlodipin substantially (90%) is metabolized by a liver with formation of inactive metabolites.
Removal. Telmisartan has the biexponetsialny nature of pharmacokinetics with terminal elimination half-life & gt, 20 hours. The maximum concentration increases in blood plasma (Cmax) and, to a lesser extent, AUC disproportionately a dose. Clinically significant cumulation of a telmisartan is not found.
After oral introduction telmisartan it is almost completely removed with a stake in not changed look. The general excretion with urine is also lt, 2% of a dose. The general plasma clearance (CLtot) high (about 900 ml/min.) in comparison with a hepatic blood-groove (about 1500 ml/min.).
Removal of an amlodipin from blood plasma happens dvukhfazno, final elimination half-life makes about 30-50 hours. Steady level in plasma is reached after constant administration of drug within 7-8 days. 10% of an initial amlodipin and 60% of its metabolites are removed with urine.
Children and teenagers up to 18 years. Pharmacokinetic data are absent.
Floor. Differences of concentration of a telmisartan in plasma depending on a floor are observed. Women have Cmax and AUC values, respectively, approximately in 3 and 2 times is higher, than at men that significantly does not affect efficiency of drug.
Patients of advanced age. The pharmacokinetics of a telmisartan does not differ between patients of advanced age and younger patients. Time of achievement of peak of concentration of an amlodipin in blood plasma it is similar at patients of young and advanced age. At patients of advanced age the clearance of an amlodipin tends to decrease, bringing in result to increase in AUC value and eliminative elimination half-life.
Patients with renal failures. At the patients with a renal failure who are on a hemodialysis the decrease in concentration of a telmisartan in blood plasma was observed. Telmisartan substantially contacts proteins of plasma and cannot be brought by dialysis. The pharmacokinetics of an amlodipin significantly does not change.
Patients with abnormal liver functions. The pharmacokinetics researches conducted at patients with abnormal liver functions showed that the absolute bioavailability of a telmisartan increased almost to 100%. Elimination half-life did not change. The clearance of an amlodipin decreased that led to increase in AUC value approximately for 40-60%.
The pharmacodynamics
of TVINSTA represents a combination of two antihypertensive substances with the complementary mechanisms of action allowing to control arterial blood pressure at patients with essential arterial hypertension: the antagonist of receptors of angiotensin II – telmisartan and a dihydropyridinic blocker of calcium channels – amlodipin.
The combination of these components provides higher level of antihypertensive effect, than reception of each of components separately.
Administration of drug of TVINSTA in therapeutic doses provides once a day an effective and smooth lowering of arterial pressure.
Telmisartan is an effective and specific (selection) antagonist of receptors of angiotensin II (AT1 type) for intake. Telmisartan with very high degree of affinity forms communication only with the AT1-subtype of receptors of angiotensin II. Telmisartan has no affinity to other receptors, including AT2 – to angiotensin receptors, and to other receptors which were less studied by AT. The functional role of these receptors is unknown, also as well as effect of their possible superstimulation by angiotensin II which levels increase thanks to a telmisartan.
Telmisartan reduces Aldosteronum level in blood plasma and angiotensin of the turning enzyme (kinase of II) to which participation there is a decrease in synthesis of bradykinin does not suppress activity. Telmisartan does not inhibit renin in plasma of the person and does not block ion channels. Therefore there is no strengthening of the side effects caused by bradykinin.
After reception of the first dose of a telmisartan the antihypertensive activity gradually becomes noticeable within 3 hours. Angiotensin II inhibition against the background of a telmisartan in a dose of 80 mg is supported more than 24 hours and remains up to 48 h. The maximum lowering of arterial pressure is gradually reached in 4 weeks after an initiation of treatment and supported during long-term treatment.
The antihypertensive effect of a telmisartan is maintained for more than 24 hours after reception, including the last 4 hours before reception of the following dose.
There is an obvious dependence of a dose on the recovery time of basic systolic arterial blood pressure concerning what data on diastolic arterial blood pressure are contradictory.
At patients with hypertensia telmisartan reduces systolic and diastolic arterial blood pressure without change of heart rate.
The antihypertensive efficiency of a telmisartan is comparable to antihypertensive drugs of other classes (that is shown in clinical trials of comparison of a telmisartan with amlodipiny, atenolol, enaliprily, a hydrochlorothiazide, lozartany, lisinopril, ramiprily and valsartany).
In case of the sudden termination of treatment telmisartany arterial blood pressure gradually returns to values before treatment within several days without signs of fast resuming of hypertensia (there is no syndrome of cancellation).
Treatment telmisartany patients with hypertensia and a hypertrophy of a left ventricle is followed by significant degrowth of a left ventricle and the index of mass of a left ventricle.
Clinical trials using such drugs of comparison as lozartan, ramiprit and valsartan showed that treatment telmisartany patients with hypertensia and a diabetic nephropathy was followed by significant reduction of a proteinuria (including, microalbuminurias and macroalbuminurias).
In clinical trials at direct comparison of two types of antihypertensive treatment the frequency of cases of dry cough at the patients accepting telmisartan was much lower, than at receiving angiotensin-converting enzyme inhibitors.
Prevention of cardiovascular complications and mortality. In the research ONTARGET (ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial) the efficiency of a telmisartan, ramipril and combination of a telmisartan and ramipril concerning cardiovascular complications at 25620 patients (aged from 55 years and is more senior) with existence in the anamnesis of coronary heart disease, a stroke, diseases of peripheral vessels or the diabetes which was followed by changes of target organs (for example, a retinopathy, a hypertrophy of a left ventricle, macro - or a microalbuminuria) was compared to involvement of patients with high karidovaskulyarny risk.
The best results were received in case of use of a telmisartan in comparison with ramiprily or a combination of a telmisartan and a ramipril though the patients participating in this research were selected on condition of good tolerance of APF inhibitors. The analysis of the adverse phenomena leading to final cancellation of treatment and the serious adverse phenomena showed that the frequency of development of cough and Quincke's disease in the patients receiving telmisartan was lower, than at the patients receiving ramiprit, however the frequency of development of hypotension, on the contrary, was higher at the patients receiving telmisartan.
The combination of a telmisartan and a ramipril did not provide the best effect in comparison with ramiprily and telmisartany separately. Besides, higher frequency of emergence of a hyperpotassemia, a renal failure, arterial hypotension and dizziness in group of the combined treatment is recorded. Therefore, in this group of patients ramiprit use of a combination and the telmisaratna is not recommended.
Amlodipin – the inhibitor of inflow of calcium ions entering into group of dihydropyridine (blockers of slow channels or antagonists of calcium ions). It inhibits transmembrane inflow of calcium ions to cells of a myocardium and cells of unstriated muscles of vessels.
The mechanism of antihypertensive action of an amlodipin consists in the direct relaxing impact on smooth muscle cells of vessels that leads to decrease in peripheric vascular resistance and arterial blood pressure, connecting to dihydropyridinic and nedegidropiridinovy places of binding. Action of an amlodipin on vessels relatively selectively, it has a greater influence on vascular smooth muscle cells, than on myocardium cells. At patients with hypertensia the use of an amlodipin provides clinically significant lowering of arterial pressure, as in a prone position, and standing, for 24 hours once a day. Owing to the slow beginning of effect of drug the acute hypotension during use of an amlodipin is not typical.
At patients with hypertensia and normal function of kidneys amlodipin in therapeutic doses led to reduction of vascular resistance of kidneys, increase in glomerular filtration rate and effective current of plasma in kidneys that was not followed by changes of fraction of filtration or a proteinuria.
Amlodipin does not result in any metabolic adverse effects or changes of lipids of plasma and therefore is suitable for use for patients with bronchial asthma, diabetes and gout.
Patients with heart failure. The studying a hemodynamics and shipping of physical activities which was carried out in controlled clinical trials at patients with heart failure of the II-IV classes on classification of NYHA was shown that amlodipin did not lead to clinical deterioration in the heart failure estimated by way of determination of tolerance to loadings, fraction of emission of a left ventricle and clinical manifestations.
The placebo-controlled research (PRAISE) at patients with heart failure of the II-IV classes on classification of NYHA accepting digoxin, diuretics and APF inhibitors showed what amlodipin does not lead to increase in mortality risk and/or incidence of heart failure.
The Efficiency and safety of drug TVINSTA in comparison with separate components of this drug were studied by TVINSTA at patients with hypertensia, insufficiently controlled monotherapy amlodipiny in a dose of 5 mg. Frequency of achievement of control over arterial blood pressure when using TVINSTA was bigger (in a dose of 80/5 mg), than when using an amlodipin in a dose of 10 mg, and the frequency of development of hypostases was significantly less.
In case of development in patients with the hypertensia which is rather controlled amlodipiny in a dose of 10 mg, the profound hypostases, use of TVINSTA in a dose of 80/5 mg is able to afford to reduce the frequency of these side effects at preservation of control over arterial blood pressure.
The antihypertensive effect of TVINSTA did not depend on age and sex of patients, and was similar at patients to existence and absence of diabetes.
Indications
- treatment of essential arterial hypertension
the Substituting therapy: the patients receiving telmisartan and amlodipin in the form of separate tablets can pass to administration of drug of TVINSTA containing the same doses of components.
Additional therapy: drug TVINSTA is shown to patients who have a monotherapy telmisartany or amlodipiny does not lead to due control of arterial blood pressure.
Initial therapy: drug TVINSTA can be used as initial therapy at patients by whom use of several drugs for achievement of necessary level of arterial blood pressure can be required. The choice of drug TVINSTA as initial therapy of hypertensia has to be based on assessment of expected advantage and risk.
Route of administration and doses
Adult patients: the drug TVINSTA is taken once a day.
The substituting therapy: the patients receiving telmisartan and amlodipin in the form of separate tablets can pass to reception TVINSTY, containing the same doses of components and to accept on one tablet once a day for convenience of therapy.
Additional therapy: TVINSTA can be appointed to patients who have a use of one amlodipin or one telmisartan does not allow to reach due control of arterial blood pressure.
The patients accepting amlodipin in a dose of 10 mg at which the side reactions limiting administration of drug, for example, hypostases are noted can pass to reception of TVINSTA in a dose 80/5 mg once a day that will allow to reduce a dose of an amlodipin, but will not reduce the cumulative expected antihypertensive effect.
Initial therapy: the patient can begin with reception of TVINSTA in case of the small probability of ensuring control of arterial blood pressure by means of one drug. The initial dose of TVINSTA makes 80/5 mg for the patients needing a considerable lowering of arterial pressure once a day.
In case of need an additional lowering of arterial pressure after 2 weeks of treatment, the dose of drug can raise gradually before achievement of the maximum dose of 80/10 mg once a day.
Drug can be used with other antihypertensive drugs.
The drug can be taken irrespective of meal.
Renal failures: to patients with renal failures, including to the patients who are on a hemodialysis, changes of drug dosing are not required. Amlodipin and telmisartan are not dialyzed.
Elderly patients: changes of dosing are not required.
Children and teenagers: drug TVINSTA is not recommended to be used to patients aged up to 18 years due to the lack of data on safety and efficiency.
Side effects
the Combination of the fixed doses: safety and tolerance of drug TVINSTA were estimated during five controlled clinical trials more than at 3500 patients, and from them received more than 2500 telmisartan in a combination with amlodipiny.
Infections and invasions: cystitis
Mental disorders: depression, concern, insomnia
of Disorder of the central nervous system: dizziness, drowsiness, migraine, a headache, paresthesias, faints, peripheral neuropathy, a giposteziya, a dysgeusia, a tremor
Disturbance from an organ of hearing and a vestibular mechanism: vertigo
Narusheniya from a cardiovascular system: bradycardia, heartbeat
Vascular disorders: hypotension, orthostatic hypotension, feeling of rush of blood to
the person Narusheniya from the respiratory system, bodies of a thorax and mediastinum: cough
Gastrointestinal disorders: an abdominal pain, diarrhea, vomiting, nausea, a hypertrophy of gums, dyspepsia, dryness in
Narusheniya's mouth from skin and hypodermic cellulose: an itching, eczema, an erythema, pour
Narusheniya from a musculoskeletal system and connective tissue: arthralgias, a dorsodynia, spasms of muscles (spasms in legs), myalgias, pain in extremities (onychalgia)
of Narusheniya of work of kidneys and urinary tract:
Narusheniya's nocturia of work of a reproductive system and disease of mammary glands: erectile dysfunction
General disorders: peripheral hypostases, asthenia (weakness), stethalgia, fatigue, indisposition
of Change of laboratory indicators: increase in content of enzymes of a liver, increase in level of uric acid in blood
Additional information concerning a combination of components: the peripheral hypostases recognized as dose-dependent side effect of an amlodipin usually are observed with a smaller frequency at the patients receiving a combination of a telmisartan and an amlodipin than at the patients receiving only amlodipin.
Additional information concerning separate components: the side effects which were earlier reported when using one of drug components (an amlodipina or a telmisartana), can amplify when using TVINSTA even if they were not observed in clinical trials or during the post-marketing period.
Telmisartan:
Infections and invasions: infections of urinary tract, upper respiratory tract infections, sepsis, including a lethal outcome
of Narusheniya from blood and lymphatic systems: anemia, an eosinophilia,
Narusheniya's thrombocytopenia from the immune system: a hyperpotassemia, a hypoglycemia (at patients with diabetes)
Narusheniya from organs of sight: disorders of vision
of Narusheniya from a cardiovascular system:
Narusheniya's tachycardia from the respiratory system, bodies of a thorax and mediastinum: asthma
Gastrointestinal disorders: an abdominal distension, discomfort in a stomach
of Disorder of a gepatobiliarny system: abnormal liver functions, changes from a liver * (a *bolshy part of cases of the abnormal liver functions observed in the post-registration period was observed at residents of Japan who are more inclined to development of such undesirable reactions).
Disturbances from skin and hypodermic cellulose: a Quincke's disease (a Quincke's edema, including from the death), a hyperhidrosis, urticaria, medicamentous rash, toxic rash
of Disturbance from a musculoskeletal system and connective tissue: sinew pain (tendinitopodobny symptoms)
of Disturbance of work of kidneys and urinary tract: renal failures, including an acute renal failure (see also section Special Instructions)
the General disorders: grippopodobny syndrome
of Change of laboratory indicators: decrease in level of hemoglobin, increase in level of creatinine and a kreatinfosfokinaza in blood (KFK)
Amlodipin:
Disturbances from blood and lymphatic systems: a leukopenia,
Disturbance thrombocytopenia from the immune system: hypersensitivity
Disbolism: hyperglycemia
Mental disorders: change of mood, confusion of consciousness
Disturbance from organs of sight: a disorder of vision
Disturbance from an organ of hearing and a vestibular mechanism: a ring in
Disturbance ears from a cardiovascular system: myocardial infarction, arrhythmia, ventricular tachycardia, fibrillation of auricles
Vascular disorders:
the Disturbance vasculitis from the respiratory system, bodies of a thorax and mediastinum: short wind, rhinitis
Gastrointestinal disorders: defecation disorders, pancreatitis, gastritis
of Disorder of a gepatobiliarny system: hepatitis, jaundice, increase in level of enzymes of a liver (mainly reflecting a cholestasia)
Disturbances from skin and hypodermic cellulose: hyperhidrosis, Quincke's disease, small tortoiseshell, alopecia, purpura, xanthopathy change, multiformny erythema, scaly dermatitis, Stephens-Johnson's syndrome, photosensitivity
of Disturbance of work of kidneys and urinary tract: urination disturbances, pollakiuria
of Disturbance of work of a reproductive system and disease of mammary glands: gynecomastia
General disturbances: pain, increase in body weight, decrease in body weight
of the Contraindication
- hypersensitivity to active agents or to any of drug components
- hypersensitivity to dihydropyridine derivatives
- obstructive diseases of bilious ways
- abnormal liver functions
- cardiogenic shock
- joint administration of drug of TVINSTA with aliskereny at patients with diabetes or a renal failure (SKF & lt, 60 ml/min. / 1.73 sq.m)
- presence of rare hereditary diseases which can be incompatible with any of drug components
- pregnancy and the period of a lactation
- children's and teenage age up to 18 years
Medicinal interactions
of Interactions between two components which are in the fixed doses a part of this drug in clinical trials was not observed.
Interactions inherent to a combination of the components which are a part of drug:
Special researches about medicinal interactions of drug TVINSTA with other drugs were not conducted.
At simultaneous use of the drugs provided below it is necessary to take the following information into account:
At simultaneous use with other antihypertensive drugs the hypotensive action of TVINSTA can amplify.
The drugs reducing arterial blood pressure: it is expected that Baclofenum and amifostin, thanks to the pharmacological properties, is strengthened by hypotensive effect of all antihypertensive drugs, including drug TVINSTA. Besides, orthostatic hypotension can amplify alcohol, barbiturates, drugs or antidepressants.
Corticosteroids (system use): decrease in antihypertensive effect is possible.
The hypotensive effect of other antihypertensive drugs can increase the interactions caused telmisartany Telmisartan. Other interactions having clinical value it is not established.
Use of a telmisartan did not lead to clinically significant interaction with digoxin, warfarin, a hydrochlorothiazide, glibenclamide, an ibuprofen, paracetamol, simvastatiny and amlodipiny. As increase in concentration of digoxin in blood plasma up to 20% was observed (in an isolated case up to 39%), it is necessary to take into account expediency of control of level of digoxin in plasma.
In one of researches it is established that simultaneous use of a telmisartan and ramipril led to increase in AUC0-24 and Cmax values of a ramipril and the ramiprilat up to 2.5 times. The clinical importance of this observation is unknown.
During simultaneous use of lithium with inhibitors of angiotensin-converting enzyme (APF) it was reported about reversible increase in concentration of lithium in serum and development of toxicity. About similar cases it was also reported at simultaneous use of antagonists of receptors of angiotensin II, including telmisartan. Therefore during combined use with these drugs the control of level of lithium in blood serum is recommended.
In case of dehydration the use of non-steroidal anti-inflammatory drugs (NPVP), including acetylsalicylic acid in anti-inflammatory doses, inhibitors of cyclooxygenase-2 and non-selective NPVP, can cause an acute renal failure. The drugs affecting activity of a system renin-angiotensin, including telmisartan can have synergy effect in this regard. At the patients receiving NPVP and telmisartan the adequate water relationships (hydration) has to be provided, and in an initiation of treatment the control of function of kidneys is necessary. At simultaneous use of NPVP and antihypertensive drugs similar to a telmisartan, it was reported about reduction of hypotensive effect owing to inhibition of prostaglandins possessing vazodilatiruyushchy action.
The interactions caused amlodipiny:
At simultaneous use of the drugs provided below it is necessary to be careful.
Grapefruit and grapefruit juice: the concomitant use of drug with grapefruit or grapefruit juice owing to the possible strengthening of bioavailability leading to strong increase in arterial blood pressure at a number of patients is not recommended.
CYP3A4 inhibitors: in a research at patients of advanced age it was shown that diltiazem inhibits metabolism of an amlodipin, possibly influencing CYP3A4 (concentration of an amlodipin in plasma increase approximately by 50% and the effect of an amlodipin amplifies). It is impossible to exclude that more active CYP3A4 inhibitors (such as ketokonazol, itrakonazol, ritonavir) can increase concentration of an amlodipin in plasma more than diltiazem.
The inductors CYP3A4 [anticonvulsant drugs (for example, carbamazepine, phenobarbital, Phenytoinum, fosfenitoin, Primidonum), the rifampicin, a St. John's wort which is made a hole: combined use can lead to decrease in concentration of an amlodipin in plasma. During use of the inductors CYP3A4 and also after their cancellation the clinical monitoring of an amlodipin with possible dose adjustment of an amlodipin is recommended.
At simultaneous use of the drugs provided below it is necessary to take the following information into account:
Simvastatin: joint reception of multiple doses of an amlodipin from 80 mg of a simvastatin increases impact of the last on 77% in comparison with its isolated reception. Thus, the day dose of a simvastatin at the patients accepting amlodipin has to be limited up to 20 mg a day.
Other drugs: at monotherapy safety of combined use of an amlodipin with thiazide diuretic, beta-blockers, APF inhibitors, nitrates of the prolonged action, the nitroglycerine (applied sublingual), non-steroidal anti-inflammatory drugs, antibiotics and oral hypoglycemic drugs is established. At simultaneous use of an amlodipin and sildenafil, each substance shows independent hypotensive action.
Additional information: the concomitant use of 240 ml of juice of grapefruit with a dose of an amlodipin of 10 mg inside does not result in significant effect on pharmacokinetic properties of an amlodipin.
Simultaneous use of an amlodipin with Cimetidinum had no significant effect on pharmacokinetics of an amlodipin.
Simultaneous use of an amlodipin with atorvastatiny, digoxin, warfarin or cyclosporine significantly did not influence pharmacokinetics or a pharmacodynamics of these drugs.
Special indications
of the Abnormal liver function: telmisartan it is removed mainly with bile. At patients with obstruction of biliary tract or a liver failure the lowered clearance can be observed. Elimination half-life of an amlodipin, similar to antagonists of calcium, can be increased at patients from the liver worsened by function and the recommended doses in this case are not defined. Use of drug TVINSTA in dosages of 80 mg / 5 is contraindicated to mg, 80 mg / 10 to mg at patients with an abnormal liver function.
Renovascular hypertensia: patients with a bilateral stenosis of renal arteries or a stenosis have arteries of the only functioning kidney, taking medicines which influence renin-angiotensin-aldosteronovuyu a system, there is an increased risk of developing heavy hypotension and renal failure.
Renal failures and a state after transplantation of a kidney: when prescribing drug TVINSTA, periodic control of levels of potassium and creatinine in blood serum is recommended to patients with renal failures. Experience of use of drug TVINSTA for patients with transplantation of kidneys in the anamnesis is absent. Telmisartan and amlodipin are not dialyzed.
Intravascular hypovolemia: at patients with a reduced volume of the circulating blood and/or the hyponatremia arising, for example, owing to intensive diuretic care, dietary restrictions of consumption of table salt, diarrhea or vomiting the symptomatic hypotension, especially after reception of the first dose of drug can develop. Before drug TVINSTA use such states have to be eliminated.
Double blockade system renin-angiotensin-aldosteronovoy: it was reported that as a result of system inhibition renin-angiotensin-Aldosteronum, especially in case of use of a combination of medicines which influence this system the predisposed patients can have renal failures (up to development of an acute renal failure). Drug TVINSTA can be used together with other antihypertensive drugs, however double blockade of a system renin-angiotensin-Aldosteronum (for example, addition of inhibitor of angiotensin-converting enzyme or direct inhibitors renin-aliskerena to the antagonist of receptors of angiotensin II) is not recommended and can be used only according to individual indications on condition of careful monitoring of function of kidneys (see the section Contraindications).
Other conditions with stimulation system renin-angiotensin-aldosteronovoy:
When the tone of vessels and function of kidneys substantially depend on activity system renin-angiotensin-aldosteronovoy, for example, at patients with the profound stagnant heart failure or with associated diseases of kidneys, including with a renal artery stenosis, use of medicines which influence a condition of this system can be followed by development of acute hypotension, a hyperazotemia, oliguria or, in rare instances, of an acute renal failure.
Primary hyper aldosteronism: patients with primary hyper aldosteronism have antihypertensive medicines operating by inhibition system renin-angiotensin-aldosteronovoy as a rule are not effective. Use of a telmisartan in such cases is not recommended.
Stenosis of aortal and mitral valves, subaortic hypertrophic stenosis: at patients with an aortal or mitral stenosis, or a subaortic hypertrophic stenosis the drug TVINSTA use, also as well as other vazodilatator, demands extra care.
Unstable stenocardia, acute myocardial infarction: the data proving use of drug TVINSTA at patients with unstable stenocardia and also in a myocardial infarction or in a month after a myocardial infarction, are not available.
Heart failure: in long placebo - a controlled research (PRAISE-2) of an amlodipin at patients with heart failure of not ischemic etiology of III and IV functional class on classification of NYHA it is established that use of an amlodipin was followed by more frequent edematization of lungs (despite the lack of essential difference in the frequency of deterioration in heart failure in comparison with placebo).
Hyperpotassemia: there is a giperkalemiya likelihood of development at treatment by the drugs influencing renin-angiotensin-aldosteronovuyu a system, especially in the presence of renal and/or heart failure. For the patients who are in a risk zone the monitoring of kcal is shown
to Develop
of Tvinsta®
the International unlicensed name
Is not present
the Dosage form
of the Tablet of 80 mg / 5 mg, 80 mg / 10 mg
Structure
One tablet contains
a layer of a telmisartan
active agent - telmisartan 80 mg,
excipients: sodium hydroxide, K25 povidone, meglumin, sorbitol, magnesium stearate
a layer of an amlodipin
active agent - an amlodipina besilat 6.935 mg or 13.870 mg (it is equivalent an amlodipina of 5 mg or 10 mg respectively)
excipients: microcrystalline cellulose, starch prezhelatinizirovanny, starch corn, silicon dioxide colloidal, mix of dyes, magnesium stearate.
Description
of the Tablet of an oval form, biconvex, two-layer: one layer from white till almost white color, other layer of blue color. On a white surface of tablets there is a logo of firm and an engraving of A3 (for a dosage of 80 mg / 5 mg), other party of a tablet smooth.
Tablets of an oval form, biconvex, two-layer: one layer from white till almost white color, other layer of blue color. On a white surface of tablets there is a logo of firm and an engraving of A4 (for a dosage of 80 mg / 10 mg), other party of a tablet smooth.
Pharmacological group
of Angiotensin II antagonists in a combination with other drugs.
Antagonists of angiotensin II and blockers of calcium channels.
Telmisartan and amlodipin.
ATH C09DB04 code
the Pharmacological
Pharmacokinetics Pharmacokinetics properties of a combination of the fixed doses
the Speed and extent of absorption of drug TVINSTA are equivalent to bioavailability of a telmisartan and an amlodipin in case of their separate use.
Pharmacokinetics of the separate
Absorption components. Absorption of a telmisartan happens quickly though amounts of the absorbed drug are various. The average absolute bioavailability of a telmisartan is about 50%. Meal slightly reduces bioavailability of a telmisartan with reduction of value of the area under a curve concentration in plasma time (AUC), varies from 6% at reception in a dose 40 mg up to 19% at reception in a dose of 160 mg. In 3 h after reception of a telmisartan its concentration in blood plasma is identical to all doses, regardless of meal. Insignificant reduction of AUC does not cause decrease in therapeutic effectiveness.
After reception of one amlodipin inside in therapeutic doses the maximum concentration in plasma is reached in 6-12 hours. The calculated absolute bioavailability is from 64% to 80%. Meal does not influence bioavailability of an amlodipin.
Distribution. Telmisartan possesses high extent of linking with proteins of plasma (& gt, 99.5%), generally with albumine and alfa-1 an acid glycoprotein. The average constant visible volume of distribution of Vss is about 500 l that indicates additional linking with fabrics.
The volume of distribution of an amlodipin is about 21 l/kg.
In the researches in vitro it is shown that at patients about 97.5% of the circulating amlodipin are connected with hypertensia with proteins of plasma.
Metabolism. Telmisartan is metabolized by conjugation with a glucuronide. The pharmacological activity of a conjugate is not found.
Amlodipin substantially (90%) is metabolized by a liver with formation of inactive metabolites.
Removal. Telmisartan has the biexponetsialny nature of pharmacokinetics with terminal elimination half-life & gt, 20 hours. The maximum concentration increases in blood plasma (Cmax) and, to a lesser extent, AUC disproportionately a dose. Clinically significant cumulation of a telmisartan is not found.
After oral introduction telmisartan it is almost completely removed with a stake in not changed look. The general excretion with urine is also lt, 2% of a dose. The general plasma clearance (CLtot) high (about 900 ml/min.) in comparison with a hepatic blood-groove (about 1500 ml/min.).
Removal of an amlodipin from blood plasma happens dvukhfazno, final elimination half-life makes about 30-50 hours. Steady level in plasma is reached after constant administration of drug within 7-8 days. 10% of an initial amlodipin and 60% of its metabolites are removed with urine.
Children and teenagers up to 18 years. Pharmacokinetic data are absent.
Floor. Differences of concentration of a telmisartan in plasma depending on a floor are observed. Women have Cmax and AUC values, respectively, approximately in 3 and 2 times is higher, than at men that significantly does not affect efficiency of drug.
Patients of advanced age. The pharmacokinetics of a telmisartan does not differ between patients of advanced age and younger patients. Time of achievement of peak of concentration of an amlodipin in blood plasma it is similar at patients of young and advanced age. At patients of advanced age the clearance of an amlodipin tends to decrease, bringing in result to increase in AUC value and eliminative elimination half-life.
Patients with renal failures. At the patients with a renal failure who are on a hemodialysis the decrease in concentration of a telmisartan in blood plasma was observed. Telmisartan substantially contacts proteins of plasma and cannot be brought by dialysis. The pharmacokinetics of an amlodipin significantly does not change.
Patients with abnormal liver functions. The pharmacokinetics researches conducted at patients with abnormal liver functions showed that the absolute bioavailability of a telmisartan increased almost to 100%. Elimination half-life did not change. The clearance of an amlodipin decreased that led to increase in AUC value approximately for 40-60%.
The pharmacodynamics
of TVINSTA represents a combination of two antihypertensive substances with the complementary mechanisms of action allowing to control arterial blood pressure at patients with essential arterial hypertension: the antagonist of receptors of angiotensin II – telmisartan and a dihydropyridinic blocker of calcium channels – amlodipin.
The combination of these components provides higher level of antihypertensive effect, than reception of each of components separately.
Administration of drug of TVINSTA in therapeutic doses provides once a day an effective and smooth lowering of arterial pressure.
Telmisartan is an effective and specific (selection) antagonist of receptors of angiotensin II (AT1 type) for intake. Telmisartan with very high degree of affinity forms communication only with the AT1-subtype of receptors of angiotensin II. Telmisartan has no affinity to other receptors, including AT2 – to angiotensin receptors, and to other receptors which were less studied by AT. The functional role of these receptors is unknown, also as well as effect of their possible superstimulation by angiotensin II which levels increase thanks to a telmisartan.
Telmisartan reduces Aldosteronum level in blood plasma and angiotensin of the turning enzyme (kinase of II) to which participation there is a decrease in synthesis of bradykinin does not suppress activity. Telmisartan does not inhibit renin in plasma of the person and does not block ion channels. Therefore there is no strengthening of the side effects caused by bradykinin.
After reception of the first dose of a telmisartan the antihypertensive activity gradually becomes noticeable within 3 hours. Angiotensin II inhibition against the background of a telmisartan in a dose of 80 mg is supported more than 24 hours and remains up to 48 h. The maximum lowering of arterial pressure is gradually reached in 4 weeks after an initiation of treatment and supported during long-term treatment.
The antihypertensive effect of a telmisartan is maintained for more than 24 hours after reception, including the last 4 hours before reception of the following dose.
There is an obvious dependence of a dose on the recovery time of basic systolic arterial blood pressure concerning what data on diastolic arterial blood pressure are contradictory.
At patients with hypertensia telmisartan reduces systolic and diastolic arterial blood pressure without change of heart rate.
The antihypertensive efficiency of a telmisartan is comparable to antihypertensive drugs of other classes (that is shown in clinical trials of comparison of a telmisartan with amlodipiny, atenolol, enaliprily, a hydrochlorothiazide, lozartany, lisinopril, ramiprily and valsartany).
In case of the sudden termination of treatment telmisartany arterial blood pressure gradually returns to values before treatment within several days without signs of fast resuming of hypertensia (there is no syndrome of cancellation).
Treatment telmisartany patients with hypertensia and a hypertrophy of a left ventricle is followed by significant degrowth of a left ventricle and the index of mass of a left ventricle.
Clinical trials using such drugs of comparison as lozartan, ramiprit and valsartan showed that treatment telmisartany patients with hypertensia and a diabetic nephropathy was followed by significant reduction of a proteinuria (including, microalbuminurias and macroalbuminurias).
In clinical trials at direct comparison of two types of antihypertensive treatment the frequency of cases of dry cough at the patients accepting telmisartan was much lower, than at receiving angiotensin-converting enzyme inhibitors.
Prevention of cardiovascular complications and mortality. In the research ONTARGET (ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial) the efficiency of a telmisartan, ramipril and combination of a telmisartan and ramipril concerning cardiovascular complications at 25620 patients (aged from 55 years and is more senior) with existence in the anamnesis of coronary heart disease, a stroke, diseases of peripheral vessels or the diabetes which was followed by changes of target organs (for example, a retinopathy, a hypertrophy of a left ventricle, macro - or a microalbuminuria) was compared to involvement of patients with high karidovaskulyarny risk.
The best results were received in case of use of a telmisartan in comparison with ramiprily or a combination of a telmisartan and a ramipril though the patients participating in this research were selected on condition of good tolerance of APF inhibitors. The analysis of the adverse phenomena leading to final cancellation of treatment and the serious adverse phenomena showed that the frequency of development of cough and Quincke's disease in the patients receiving telmisartan was lower, than at the patients receiving ramiprit, however the frequency of development of hypotension, on the contrary, was higher at the patients receiving telmisartan.
The combination of a telmisartan and a ramipril did not provide the best effect in comparison with ramiprily and telmisartany separately. Besides, higher frequency of emergence of a hyperpotassemia, a renal failure, arterial hypotension and dizziness in group of the combined treatment is recorded. Therefore, in this group of patients ramiprit use of a combination and the telmisaratna is not recommended.
Amlodipin – the inhibitor of inflow of calcium ions entering into group of dihydropyridine (blockers of slow channels or antagonists of calcium ions). It inhibits transmembrane inflow of calcium ions to cells of a myocardium and cells of unstriated muscles of vessels.
The mechanism of antihypertensive action of an amlodipin consists in the direct relaxing impact on smooth muscle cells of vessels that leads to decrease in peripheric vascular resistance and arterial blood pressure, connecting to dihydropyridinic and nedegidropiridinovy places of binding. Action of an amlodipin on vessels relatively selectively, it has a greater influence on vascular smooth muscle cells, than on myocardium cells. At patients with hypertensia the use of an amlodipin provides clinically significant lowering of arterial pressure, as in a prone position, and standing, for 24 hours once a day. Owing to the slow beginning of effect of drug the acute hypotension during use of an amlodipin is not typical.
At patients with hypertensia and normal function of kidneys amlodipin in therapeutic doses led to reduction of vascular resistance of kidneys, increase in glomerular filtration rate and effective current of plasma in kidneys that was not followed by changes of fraction of filtration or a proteinuria.
Amlodipin does not result in any metabolic adverse effects or changes of lipids of plasma and therefore is suitable for use for patients with bronchial asthma, diabetes and gout.
Patients with heart failure. The studying a hemodynamics and shipping of physical activities which was carried out in controlled clinical trials at patients with heart failure of the II-IV classes on classification of NYHA was shown that amlodipin did not lead to clinical deterioration in the heart failure estimated by way of determination of tolerance to loadings, fraction of emission of a left ventricle and clinical manifestations.
The placebo-controlled research (PRAISE) at patients with heart failure of the II-IV classes on classification of NYHA accepting digoxin, diuretics and APF inhibitors showed what amlodipin does not lead to increase in mortality risk and/or incidence of heart failure.
The Efficiency and safety of drug TVINSTA in comparison with separate components of this drug were studied by TVINSTA at patients with hypertensia, insufficiently controlled monotherapy amlodipiny in a dose of 5 mg. Frequency of achievement of control over arterial blood pressure when using TVINSTA was bigger (in a dose of 80/5 mg), than when using an amlodipin in a dose of 10 mg, and the frequency of development of hypostases was significantly less.
In case of development in patients with the hypertensia which is rather controlled amlodipiny in a dose of 10 mg, the profound hypostases, use of TVINSTA in a dose of 80/5 mg is able to afford to reduce the frequency of these side effects at preservation of control over arterial blood pressure.
The antihypertensive effect of TVINSTA did not depend on age and sex of patients, and was similar at patients to existence and absence of diabetes.
Indications
- treatment of essential arterial hypertension
the Substituting therapy: the patients receiving telmisartan and amlodipin in the form of separate tablets can pass to administration of drug of TVINSTA containing the same doses of components.
Additional therapy: drug TVINSTA is shown to patients who have a monotherapy telmisartany or amlodipiny does not lead to due control of arterial blood pressure.
Initial therapy: drug TVINSTA can be used as initial therapy at patients by whom use of several drugs for achievement of necessary level of arterial blood pressure can be required. The choice of drug TVINSTA as initial therapy of hypertensia has to be based on assessment of expected advantage and risk.
Route of administration and doses
Adult patients: the drug TVINSTA is taken once a day.
The substituting therapy: the patients receiving telmisartan and amlodipin in the form of separate tablets can pass to reception TVINSTY, containing the same doses of components and to accept on one tablet once a day for convenience of therapy.
Additional therapy: TVINSTA can be appointed to patients who have a use of one amlodipin or one telmisartan does not allow to reach due control of arterial blood pressure.
The patients accepting amlodipin in a dose of 10 mg at which the side reactions limiting administration of drug, for example, hypostases are noted can pass to reception of TVINSTA in a dose 80/5 mg once a day that will allow to reduce a dose of an amlodipin, but will not reduce the cumulative expected antihypertensive effect.
Initial therapy: the patient can begin with reception of TVINSTA in case of the small probability of ensuring control of arterial blood pressure by means of one drug. The initial dose of TVINSTA makes 80/5 mg for the patients needing a considerable lowering of arterial pressure once a day.
In case of need an additional lowering of arterial pressure after 2 weeks of treatment, the dose of drug can raise gradually before achievement of the maximum dose of 80/10 mg once a day.
Drug can be used with other antihypertensive drugs.
The drug can be taken irrespective of meal.
Renal failures: to patients with renal failures, including to the patients who are on a hemodialysis, changes of drug dosing are not required. Amlodipin and telmisartan are not dialyzed.
Elderly patients: changes of dosing are not required.
Children and teenagers: drug TVINSTA is not recommended to be used to patients aged up to 18 years due to the lack of data on safety and efficiency.
Side effects
the Combination of the fixed doses: safety and tolerance of drug TVINSTA were estimated during five controlled clinical trials more than at 3500 patients, and from them received more than 2500 telmisartan in a combination with amlodipiny.
Infections and invasions: cystitis
Mental disorders: depression, concern, insomnia
of Disorder of the central nervous system: dizziness, drowsiness, migraine, a headache, paresthesias, faints, peripheral neuropathy, a giposteziya, a dysgeusia, a tremor
Disturbance from an organ of hearing and a vestibular mechanism: vertigo
Narusheniya from a cardiovascular system: bradycardia, heartbeat
Vascular disorders: hypotension, orthostatic hypotension, feeling of rush of blood to
the person Narusheniya from the respiratory system, bodies of a thorax and mediastinum: cough
Gastrointestinal disorders: an abdominal pain, diarrhea, vomiting, nausea, a hypertrophy of gums, dyspepsia, dryness in
Narusheniya's mouth from skin and hypodermic cellulose: an itching, eczema, an erythema, pour
Narusheniya from a musculoskeletal system and connective tissue: arthralgias, a dorsodynia, spasms of muscles (spasms in legs), myalgias, pain in extremities (onychalgia)
of Narusheniya of work of kidneys and urinary tract:
Narusheniya's nocturia of work of a reproductive system and disease of mammary glands: erectile dysfunction
General disorders: peripheral hypostases, asthenia (weakness), stethalgia, fatigue, indisposition
of Change of laboratory indicators: increase in content of enzymes of a liver, increase in level of uric acid in blood
Additional information concerning a combination of components: the peripheral hypostases recognized as dose-dependent side effect of an amlodipin usually are observed with a smaller frequency at the patients receiving a combination of a telmisartan and an amlodipin than at the patients receiving only amlodipin.
Additional information concerning separate components: the side effects which were earlier reported when using one of drug components (an amlodipina or a telmisartana), can amplify when using TVINSTA even if they were not observed in clinical trials or during the post-marketing period.
Telmisartan:
Infections and invasions: infections of urinary tract, upper respiratory tract infections, sepsis, including a lethal outcome
of Narusheniya from blood and lymphatic systems: anemia, an eosinophilia,
Narusheniya's thrombocytopenia from the immune system: a hyperpotassemia, a hypoglycemia (at patients with diabetes)
Narusheniya from organs of sight: disorders of vision
of Narusheniya from a cardiovascular system:
Narusheniya's tachycardia from the respiratory system, bodies of a thorax and mediastinum: asthma
Gastrointestinal disorders: an abdominal distension, discomfort in a stomach
of Disorder of a gepatobiliarny system: abnormal liver functions, changes from a liver * (a *bolshy part of cases of the abnormal liver functions observed in the post-registration period was observed at residents of Japan who are more inclined to development of such undesirable reactions).
Disturbances from skin and hypodermic cellulose: a Quincke's disease (a Quincke's edema, including from the death), a hyperhidrosis, urticaria, medicamentous rash, toxic rash
of Disturbance from a musculoskeletal system and connective tissue: sinew pain (tendinitopodobny symptoms)
of Disturbance of work of kidneys and urinary tract: renal failures, including an acute renal failure (see also section Special Instructions)
the General disorders: grippopodobny syndrome
of Change of laboratory indicators: decrease in level of hemoglobin, increase in level of creatinine and a kreatinfosfokinaza in blood (KFK)
Amlodipin:
Disturbances from blood and lymphatic systems: a leukopenia,
Disturbance thrombocytopenia from the immune system: hypersensitivity
Disbolism: hyperglycemia
Mental disorders: change of mood, confusion of consciousness
Disturbance from organs of sight: a disorder of vision
Disturbance from an organ of hearing and a vestibular mechanism: a ring in
Disturbance ears from a cardiovascular system: myocardial infarction, arrhythmia, ventricular tachycardia, fibrillation of auricles
Vascular disorders:
the Disturbance vasculitis from the respiratory system, bodies of a thorax and mediastinum: short wind, rhinitis
Gastrointestinal disorders: defecation disorders, pancreatitis, gastritis
of Disorder of a gepatobiliarny system: hepatitis, jaundice, increase in level of enzymes of a liver (mainly reflecting a cholestasia)
Disturbances from skin and hypodermic cellulose: hyperhidrosis, Quincke's disease, small tortoiseshell, alopecia, purpura, xanthopathy change, multiformny erythema, scaly dermatitis, Stephens-Johnson's syndrome, photosensitivity
of Disturbance of work of kidneys and urinary tract: urination disturbances, pollakiuria
of Disturbance of work of a reproductive system and disease of mammary glands: gynecomastia
General disturbances: pain, increase in body weight, decrease in body weight
of the Contraindication
- hypersensitivity to active agents or to any of drug components
- hypersensitivity to dihydropyridine derivatives
- obstructive diseases of bilious ways
- abnormal liver functions
- cardiogenic shock
- joint administration of drug of TVINSTA with aliskereny at patients with diabetes or a renal failure (SKF & lt, 60 ml/min. / 1.73 sq.m)
- presence of rare hereditary diseases which can be incompatible with any of drug components
- pregnancy and the period of a lactation
- children's and teenage age up to 18 years
Medicinal interactions
of Interactions between two components which are in the fixed doses a part of this drug in clinical trials was not observed.
Interactions inherent to a combination of the components which are a part of drug:
Special researches about medicinal interactions of drug TVINSTA with other drugs were not conducted.
At simultaneous use of the drugs provided below it is necessary to take the following information into account:
At simultaneous use with other antihypertensive drugs the hypotensive action of TVINSTA can amplify.
The drugs reducing arterial blood pressure: it is expected that Baclofenum and amifostin, thanks to the pharmacological properties, is strengthened by hypotensive effect of all antihypertensive drugs, including drug TVINSTA. Besides, orthostatic hypotension can amplify alcohol, barbiturates, drugs or antidepressants.
Corticosteroids (system use): decrease in antihypertensive effect is possible.
The hypotensive effect of other antihypertensive drugs can increase the interactions caused telmisartany Telmisartan. Other interactions having clinical value it is not established.
Use of a telmisartan did not lead to clinically significant interaction with digoxin, warfarin, a hydrochlorothiazide, glibenclamide, an ibuprofen, paracetamol, simvastatiny and amlodipiny. As increase in concentration of digoxin in blood plasma up to 20% was observed (in an isolated case up to 39%), it is necessary to take into account expediency of control of level of digoxin in plasma.
In one of researches it is established that simultaneous use of a telmisartan and ramipril led to increase in AUC0-24 and Cmax values of a ramipril and the ramiprilat up to 2.5 times. The clinical importance of this observation is unknown.
During simultaneous use of lithium with inhibitors of angiotensin-converting enzyme (APF) it was reported about reversible increase in concentration of lithium in serum and development of toxicity. About similar cases it was also reported at simultaneous use of antagonists of receptors of angiotensin II, including telmisartan. Therefore during combined use with these drugs the control of level of lithium in blood serum is recommended.
In case of dehydration the use of non-steroidal anti-inflammatory drugs (NPVP), including acetylsalicylic acid in anti-inflammatory doses, inhibitors of cyclooxygenase-2 and non-selective NPVP, can cause an acute renal failure. The drugs affecting activity of a system renin-angiotensin, including telmisartan can have synergy effect in this regard. At the patients receiving NPVP and telmisartan the adequate water relationships (hydration) has to be provided, and in an initiation of treatment the control of function of kidneys is necessary. At simultaneous use of NPVP and antihypertensive drugs similar to a telmisartan, it was reported about reduction of hypotensive effect owing to inhibition of prostaglandins possessing vazodilatiruyushchy action.
The interactions caused amlodipiny:
At simultaneous use of the drugs provided below it is necessary to be careful.
Grapefruit and grapefruit juice: the concomitant use of drug with grapefruit or grapefruit juice owing to the possible strengthening of bioavailability leading to strong increase in arterial blood pressure at a number of patients is not recommended.
CYP3A4 inhibitors: in a research at patients of advanced age it was shown that diltiazem inhibits metabolism of an amlodipin, possibly influencing CYP3A4 (concentration of an amlodipin in plasma increase approximately by 50% and the effect of an amlodipin amplifies). It is impossible to exclude that more active CYP3A4 inhibitors (such as ketokonazol, itrakonazol, ritonavir) can increase concentration of an amlodipin in plasma more than diltiazem.
The inductors CYP3A4 [anticonvulsant drugs (for example, carbamazepine, phenobarbital, Phenytoinum, fosfenitoin, Primidonum), the rifampicin, a St. John's wort which is made a hole: combined use can lead to decrease in concentration of an amlodipin in plasma. During use of the inductors CYP3A4 and also after their cancellation the clinical monitoring of an amlodipin with possible dose adjustment of an amlodipin is recommended.
At simultaneous use of the drugs provided below it is necessary to take the following information into account:
Simvastatin: joint reception of multiple doses of an amlodipin from 80 mg of a simvastatin increases impact of the last on 77% in comparison with its isolated reception. Thus, the day dose of a simvastatin at the patients accepting amlodipin has to be limited up to 20 mg a day.
Other drugs: at monotherapy safety of combined use of an amlodipin with thiazide diuretic, beta-blockers, APF inhibitors, nitrates of the prolonged action, the nitroglycerine (applied sublingual), non-steroidal anti-inflammatory drugs, antibiotics and oral hypoglycemic drugs is established. At simultaneous use of an amlodipin and sildenafil, each substance shows independent hypotensive action.
Additional information: the concomitant use of 240 ml of juice of grapefruit with a dose of an amlodipin of 10 mg inside does not result in significant effect on pharmacokinetic properties of an amlodipin.
Simultaneous use of an amlodipin with Cimetidinum had no significant effect on pharmacokinetics of an amlodipin.
Simultaneous use of an amlodipin with atorvastatiny, digoxin, warfarin or cyclosporine significantly did not influence pharmacokinetics or a pharmacodynamics of these drugs.
Special indications
of the Abnormal liver function: telmisartan it is removed mainly with bile. At patients with obstruction of biliary tract or a liver failure the lowered clearance can be observed. Elimination half-life of an amlodipin, similar to antagonists of calcium, can be increased at patients from the liver worsened by function and the recommended doses in this case are not defined. Use of drug TVINSTA in dosages of 80 mg / 5 is contraindicated to mg, 80 mg / 10 to mg at patients with an abnormal liver function.
Renovascular hypertensia: patients with a bilateral stenosis of renal arteries or a stenosis have arteries of the only functioning kidney, taking medicines which influence renin-angiotensin-aldosteronovuyu a system, there is an increased risk of developing heavy hypotension and renal failure.
Renal failures and a state after transplantation of a kidney: when prescribing drug TVINSTA, periodic control of levels of potassium and creatinine in blood serum is recommended to patients with renal failures. Experience of use of drug TVINSTA for patients with transplantation of kidneys in the anamnesis is absent. Telmisartan and amlodipin are not dialyzed.
Intravascular hypovolemia: at patients with a reduced volume of the circulating blood and/or the hyponatremia arising, for example, owing to intensive diuretic care, dietary restrictions of consumption of table salt, diarrhea or vomiting the symptomatic hypotension, especially after reception of the first dose of drug can develop. Before drug TVINSTA use such states have to be eliminated.
Double blockade system renin-angiotensin-aldosteronovoy: it was reported that as a result of system inhibition renin-angiotensin-Aldosteronum, especially in case of use of a combination of medicines which influence this system the predisposed patients can have renal failures (up to development of an acute renal failure). Drug TVINSTA can be used together with other antihypertensive drugs, however double blockade of a system renin-angiotensin-Aldosteronum (for example, addition of inhibitor of angiotensin-converting enzyme or direct inhibitors renin-aliskerena to the antagonist of receptors of angiotensin II) is not recommended and can be used only according to individual indications on condition of careful monitoring of function of kidneys (see the section Contraindications).
Other conditions with stimulation system renin-angiotensin-aldosteronovoy:
When the tone of vessels and function of kidneys substantially depend on activity system renin-angiotensin-aldosteronovoy, for example, at patients with the profound stagnant heart failure or with associated diseases of kidneys, including with a renal artery stenosis, use of medicines which influence a condition of this system can be followed by development of acute hypotension, a hyperazotemia, oliguria or, in rare instances, of an acute renal failure.
Primary hyper aldosteronism: patients with primary hyper aldosteronism have antihypertensive medicines operating by inhibition system renin-angiotensin-aldosteronovoy as a rule are not effective. Use of a telmisartan in such cases is not recommended.
Stenosis of aortal and mitral valves, subaortic hypertrophic stenosis: at patients with an aortal or mitral stenosis, or a subaortic hypertrophic stenosis the drug TVINSTA use, also as well as other vazodilatator, demands extra care.
Unstable stenocardia, acute myocardial infarction: the data proving use of drug TVINSTA at patients with unstable stenocardia and also in a myocardial infarction or in a month after a myocardial infarction, are not available.
Heart failure: in long placebo - a controlled research (PRAISE-2) of an amlodipin at patients with heart failure of not ischemic etiology of III and IV functional class on classification of NYHA it is established that use of an amlodipin was followed by more frequent edematization of lungs (despite the lack of essential difference in the frequency of deterioration in heart failure in comparison with placebo).
Hyperpotassemia: there is a giperkalemiya likelihood of development at treatment by the drugs influencing renin-angiotensin-aldosteronovuyu a system, especially in the presence of renal and/or heart failure. For the patients who are in a risk zone the monitoring of kcal is shown
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