Description
Release form
Tablets
Pharmacological action of
Pharmacodynamics of
Telmisartan is a specific angiotensin II receptor antagonist (ARAP) (type ATi), effective when taken orally. Telmisartan has a very high affinity for AT – receptors, through which the action of angiotensin II is realized. It displaces angiotensin II from the connection with the receptor, not possessing the action of an agonist in relation to this receptor. Telmisartan binds only to the subtype of angiotensin II AT – receptors. Communication is sustainable. Telmisartan does not have an affinity for other receptors, including the AT2 receptor and other less studied angiotensin receptors. The functional significance of these receptors, as well as the effect of their possible excessive stimulation with angiotensin II, the concentration of which increases with the appointment of telmisartan, has not been studied. Telmisartan reduces the concentration of aldosterone in blood plasma, does not reduce the activity of renin, and does not block ion channels. Telmisartan does not inhibit the angiotensin converting enzyme (ACE) (kininase II), which also catalyzes the destruction of bradykinin. This avoids the side effects associated with the action of bradykinin (for example, dry cough).
Essential hypertension
In patients with a dose of 80 mg, telmisartan completely blocks the hypertensive effect of angiotensin II. The onset of antihypertensive action is noted within 3 hours after the first administration of telmisartan. The effect of the drug lasts for 24 hours and remains clinically significant until 48 hours. A pronounced antihypertensive effect usually develops 4-8 weeks after regular use.
In patients with arterial hypertension, telmisartan lowers systolic and diastolic blood pressure (BP) without affecting heart rate (HR).
In the case of a sharp cessation of telmisartan, blood pressure gradually returns to its original level over several days without the development of a withdrawal syndrome.
As shown by the results of comparative clinical studies, the antihypertensive effect of telmisartan is comparable to the antihypertensive effect of drugs of other classes (amlodipine, atenolol, enalapril, hydrochlorothiazide and lisinopril).
The incidence of dry cough was significantly lower with telmisartan compared to ACE inhibitors.
Prevention of cardiovascular disease
In patients 55 years of age and older with coronary heart disease, stroke, transient ischemic attack, peripheral arterial damage, or with complications of type 2 diabetes (for example, retinopathy, left ventricular hypertrophy, macro- or microalbuminuria) in the history of those at risk of cardiovascular events, telmisartan had an effect similar to that of ramipril in reducing the combined endpoint: non-fatal cardiovascular mortality from myocardial infarction, non-fatal stroke and hospitalization due to chronic heart failure.
Telmisartan was as effective as ramipril in reducing the incidence of secondary points: cardiovascular mortality, non-fatal myocardial infarction, or non-fatal stroke. Dry cough and angioedema were less often described with telmisartan compared with ramipril, while arterial hypotension more often occurred with telmisartan.
Pediatric and Adolescent Patients
Safety and efficacy of telmisartan in children and adolescents under 18 years of age have not been established.
Pharmacokinetics
Absorption
When taken orally, telmisartan is rapidly absorbed from the gastrointestinal tract. Bioavailability is 50%. When taken simultaneously with food, the decrease in AUC (area under the concentration-time curve) ranges from 6% (at a dose of 40 mg) to 19% (at a dose of 160 mg). After 3 hours after administration, the concentration in the blood plasma is equalized, independently, telmisartan was taken simultaneously with food or not. There is a difference in plasma concentrations in men and women. Stach (maximum concentration) and AUC were approximately 3 and 2 times, respectively, higher in women compared with men without a significant effect on effectiveness.
There is no linear relationship between the dose of the drug and its plasma concentration. Stach and, to a lesser extent, AUC increase disproportionately to increasing the dose when using doses above 40 mg per day.
Distribution of
Telmisartan is strongly bound to plasma proteins (> 99, 5%) mainly with albumin and alpha-1 acid glycoprotein. The average apparent volume of distribution (Vdss) in equilibrium is approximately 500 L.
Metabolism
Metabolized by conjugation with glucuronic acid. The conjugate does not have pharmacological activity.
Excretion
The elimination half-life (T. / 2) is more than 20 hours. It is excreted through the intestine unchanged, excretion by the kidneys – less than 1%. The total plasma clearance is high (about 1000 ml / min) compared with the “hepatic” blood flow (about 1500 ml / min).
Contraindications
– obstructive biliary tract disease
– severe hepatic impairment (class C according to the Child-Pugh classification)
– combined use with aliskiren in patients with diabetes mellitus or severe renal impairment (GFR less than 60 ml / min / 1. 73 m2 body surface area)
– simultaneous use with ACE inhibitors in patients with diabetic nephropathy
– hereditary fructose intolerance (due to the presence of sorbitol in the composition of the drug)
– pregnancy
– breastfeeding
– age up to 18 years (effectiveness and safety not established)
– hypersensitivity to the active substance or any excipients of the drug.
Caution is advised to prescribe a drug for bilateral renal artery stenosis or artery stenosis of a single functioning kidney impaired renal functionand moderate impaired liver function, a decrease in BCC against the background of previous diuretics, restriction of consumption of table salt, diarrhea or vomiting of hyponatremia, hyperkalemia, condition after kidney transplantation (no experience with use) of severe chronic heart failure, aortic and mitral valve stenosis, hypertrophic obstructive cardiomyopathy, primary hyperaldosteronism not established) patients of the Negroid race.
Pregnancy and lactation
There is currently no reliable information on the safety of telmisartan in pregnant women. In animal studies, reproductive toxicity of the drug has been identified. The use of Telzap is contraindicated during pregnancy.
If long-term treatment with Telzap is necessary, patients planning a pregnancy should choose an alternative antihypertensive drug with a proven safety profile for use during pregnancy. After establishing the fact of pregnancy, treatment with Telzap should be stopped immediately and alternative treatment should be started if necessary.
According to the results of clinical observations, the use of angiotensin II receptor antagonists in the second and third trimesters of pregnancy has a toxic effect on the fetus (impaired renal function, oligohydramnios, delayed ossification of the skull) and the newborn (renal failure, hypotension and hyperkalemia). When using angiotensin II receptor antagonists in the second trimester of pregnancy, ultrasound of the kidneys and skull of the fetus is recommended. Children mothers who took angiotensin II receptor antagonists during pregnancy should be carefully monitored to detect arterial hypotension.
Information on the use of telmisartan during breastfeeding is not available. The use of the drug Telzap during breastfeeding is contraindicated. An alternative antihypertensive drug with a more favorable safety profile should be used, especially when feeding a newborn or premature baby.
Special instructions
Impaired liver function
Use of Telzap is contraindicated in patients with cholestasis, biliary obstruction or severe liver dysfunction (class C classification) , since telmisartan is mainly excreted in the bile. It is believed that such patients have reduced hepatic clearance of telmisartan. In patients with mild or moderate degree of impaired liver function (class A and B according to the Child-Pugh classification), Telzap should be used with caution.
Renovascular hypertension
In patients with bilateral renal artery stenosis or artery stenosis of a single functioning kidney, treatment with drugs acting on RAAS increases the risk of severe arterial hypotension and renal failure.
Impaired renal function and kidney transplantation
When using Telzap in patients with impaired renal function, periodic monitoring of plasma potassium and creatinine is recommended. There is no clinical experience with Telzap in patients who have recently undergone kidney transplantation.
Decreased bcc
Symptomatic arterial hypotension, especially after the first intake of the drug, Telzap may occur in patients with a low BCC and / or sodium in the blood plasma against the background of previous treatment with diuretics, restrictions on the intake of salt, diarrhea or vomiting. Similar conditions (fluid and / or sodium deficiency) should be eliminated before taking Telzap.
Double blockade of RAAS
Concomitant use of telmisartan with aliskiren is contraindicated in patients with diabetes mellitus or renal failure (GFR less than 60 ml / min / 1.73 m2 of body surface area).
The simultaneous use of telmisartan and ACE inhibitors is contraindicated in patients with diabetic nephropathy.
As a result of inhibition of RAAS, arterial hypotension, fainting, hyperkalemia, and impaired renal function (including acute renal failure) in patients predisposed to this, especially when the combined use of several drugs also acting on this system. Therefore, a double blockade of RAAS (for example, while taking telmisartan with other RAAS antagonists) is not recommended.
In cases of dependence of vascular tone and renal function mainly on RAAS activity (for example, in patients with chronic heart failure or kidney disease, including with renal artery stenosis or stenosis of a single kidney artery), prescribing drugs that affect this system, may be accompanied by the development of acute arterial hypotension, hyperazotemia, oliguria, and in rare cases, acute renal failure.
Primary hyperaldosteronism
In patients with primary hyperaldosteronism, treatment with antihypertensive drugs, which act by suppressing RAAS, is usually ineffective. In this regard, the use of Telzap is not recommended.
Aortic and mitral valve stenosis, hypertrophic obstructive cardiomyopathy
As with other vasodilators, patients with aortic or mitral stenosis, as well as hypertrophic obstructive cardiomyopathy, should be especially careful when using Telzap.
Patients with diabetes who received insulin or hypoglycemic agents for oral administration
Hypoglycemia may occur in these patients during treatment with Telzap. Glycemia control should be strengthened, as there may be a need for dose adjustment of insulin or a hypoglycemic agent.
Hyperkalemia
The use of drugs acting on the RAAS can cause hyperkalemia. In elderly patients, patients with renal failure or diabetes mellitus, patients taking medications that increase plasma potassium levels, and / or patients with concomitant diseases, hyperkalemia can be fatal.
When deciding on the concomitant use of drugs acting on the RAAS, it is necessary to assess the ratio of risk and benefit. The main risk factors for hyperkalemia that should be considered are:
– diabetes mellitus, renal failure, age (patients older than 70 years)
is a combination with one or more drugs acting on the RAAS and / or potassium-containing food additives. Medicinal products or therapeutic classes of drugs that can cause hyperkalemia are salt substitutes containing potassium, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, NSAIDs (including selective COX-2 inhibitors), heparin, immunosuppressants (cyclosporine or tacrolimus) and trimethoprim
– intercurrent diseases, especially dehydration, acute heart failure, metabolic acidosis, impaired renal function, cytolysis syndrome (e.g. acute I am limb ischemia, rhabdomyolysis, extensive trauma).
Patients at risk are advised to carefully monitor their potassium in the blood plasma.
Sorbitol
The drug Telzap contains sorbitol (E420). Patients with rare hereditary fructose intolerance should not take the drug.
Ethnic differences
As noted for ACE inhibitors, telmisartan and other angiotensin II receptor antagonists appear to lower blood pressure in patients of the Negroid race than in other races, possibly due to a greater predisposition to lower renin activity in the patient population .
Other
As with other antihypertensive drugs, an excessive decrease in blood pressure in patients with ischemic cardiomyopathy or coronary heart disease can lead to the development of myocardial infarction or stroke.
Influence on the ability to drive vehicles and control mechanisms
Special clinical studies to study the effect of the drug on the ability to drive a car and mechanisms have not been conducted. When driving and working with mechanisms that require increased concentration of attention, care should be taken, as dizziness and drowsiness may rarely occur with the use of Telzap.
Composition of
Each 40 mg tablet contains:
active ingredient: telmisartan – 40,000 mg auxiliary
substances: meglumine – 12,000 mg, sorbitol – 162,200 mg, sodium hydroxide -3,400 mg, povidone 25 – 20,000 mg, magnesium stearate – 2,400 mg.
Each 80 mg tablet contains: active ingredient: telmisartan – 80,000 mg
excipients: meglumine – 24,000 mg, sorbitol – 324,400 mg, sodium hydroxide – 6,800 mg, povidone 25 – 40,000 mg, magnesium stearate – 4,800 mg.
Side effects
According to the WHO, unwanted effects are classified according to their frequency of development as follows: very often (? 1/10), often (from? 1/100 to <1/10), infrequently (from? 1/1000 up to <1/100), rarely (from? 1/10 000 to <1/1000), very rarely (<1/10 000) the frequency is unknown - according to the available data, it was not possible to establish the frequency of occurrence. Within each group, according to the frequency of occurrence, adverse reactions are presented in decreasing order of severity. Infectious and parasitic diseases: infrequently – urinary tract infections, including cystitis, upper respiratory tract infections, including pharyngitis and sinusitis, rarely – sepsis, incl. fatal. From the hemopoietic system: infrequently – anemia rarely – eosinophilia, thrombocytopenia. From the side of the immune system: rarely – anaphylactic reaction, hypersensitivity. From the side of metabolism: infrequently – hyperkalemia rarely – hypoglycemia (in patients with diabetes mellitus). Mental disorders: infrequently – insomnia, depression rarely – anxiety. From the nervous system: infrequently – fainting rarely – drowsiness. From the side of the organ of vision: rarely – visual disturbances. On the part of the organ of hearing and labyrinth disorders: infrequently – vertigo. From the cardiovascular system: infrequently – bradycardia, marked decrease in blood pressure, orthostatic hypotension rarely – tachycardia. From the respiratory system: infrequently – shortness of breath, cough very rarely – interstitial lung disease. From the gastrointestinal tract: infrequently – abdominal pain, diarrhea, dyspepsia, flatulence, vomiting rarely – dry mouth, discomfort in the stomach, violation of taste sensations. From the liver and biliary tract: rarely – impaired liver function / liver damage. From the skin and subcutaneous tissues: infrequently – itchy skin, hyperhidrosis, rash rarely – angioedema (also fatal), eczema, erythema, urticaria, drug rash, toxic skin rash. From the musculoskeletal system: infrequently – sciatica, muscle cramps, myalgia rarely – arthralgia, pain in the extremities, tendon-like syndrome. From the urinary system: infrequently – impaired renal function, including acute renal failure. On the part of laboratory and instrumental studies: infrequently – an increase in plasma creatinine concentrations rarely – a decrease in hemoglobin, an increase in uric acid in blood plasma, an increase in the activity of liver enzymes and CPK. Other: infrequently – chest pain, asthenia rarely – flu-like syndrome. Drug Interactions Double Blockade of the Daryngine-Angiotensin-Aldosterone System (RAAS) The concomitant use of telmisartan with aliskiren is contraindicated in patients with diabetes mellitus or renal failure (GFR less than 60 ml / min / 1.73 m2 of other body surfaces). The simultaneous use of telmisartan and ACE inhibitors is contraindicated in patients with diabetic nephropathy (see section “Contraindications”). Clinical studies have shown that double blockade of RAAS due to the combined use of ACE, ARAP, or aliskiren inhibitors is associated with an increased incidence of adverse events such as arterial hypotension, hyperkalemia and impaired renal function (including acute renal failure) in comparison with the use of only one drug acting on RAAS. The risk of developing hyperkalemia may increase when used together with other drugs that can cause hyperkalemia (potassium-containing food additives and salt substitutes containing potassium, potassium-sparing diuretics (e.g. spironolactone, eplerenone, triamterene or amiloride), non-steroidal anti-inflammatory drugs ( cyclooxygenase-2 inhibitors (COX-2)), heparin, immunosuppressants (cyclosporine or tacrolimus), and trimethoprim). If necessary, against the background of documented hypokalemia, the combined use of drugs should be carried out with caution and regularly monitor the content of potassium in the blood plasma. Digoxin When co-administered with telmisartan and digoxin, an average increase in Stax digoxin in plasma by 49% and a minimum concentration of 20% was noted. At the beginning of treatment, when selecting a dose and discontinuing treatment with telmisartan, the concentration of digoxin in blood plasma should be carefully monitored to maintain it within the therapeutic range. Potassium-sparing diuretics or potassium-containing food additives Angiotensin II receptor antagonists, such as telmisartan, reduce the loss of potassium caused by the diuretic. Potassium-sparing diuretics, for example, spironolactone, eplerenone, triamteren or amiloride, potassium-containing nutritional supplements or salt substitutes can lead to a significant increase in plasma potassium. If concomitant use is indicated, since there is documented hypokalemia, they should be used with caution and against the background of regular monitoring of potassium in the blood plasma. Lithium preparations When combined with lithium preparations with ACE and ARAP inhibitors, including telmisartan, a reversible increase in plasma lithium concentrations and its toxic effect occurred. If you need to use this combination of drugs, it is recommended that you carefully monitor the concentration of lithium in blood plasma. Nonsteroidal anti-inflammatory drugs (NSAIDs) NSAIDs (i.e. acetylsalicylic acid in doses used for anti-inflammatory treatment, COX-2 inhibitors and non-selective NSAIDs) can weaken the antihypertensive effect of ARAP. In some patients with impaired renal function (e.g., patients with dehydration, elderly patients with impaired renal function), the combined use of ARAP and drugs that inhibit cyclooxygenase -2 can lead to further deterioration of renal function, including the development of acute renal failure, which usually is reversible. Therefore, the combined use of drugs should be carried out with caution, especially in elderly patients. Adequate fluid intake should be ensured, in addition, at the beginning of joint use and periodically in the future, renal function indicators should be monitored. Diuretics (thiazide or loop ) Previous treatment with high doses of diuretics, such as furosemide ( loop diuretic) and hydrochlorothiazide (thiazide diuretic), can lead to hypovolemia and the risk of hypotension at the beginning of treatment with telmisartan. Other antihypertensive drugs The effect of telmisartan may be enhanced by the combined use of other antihypertensive drugs. Based on the pharmacological properties of baclofen and amifostine, it can be assumed that they will enhance the therapeutic effect of all antihypertensive drugs, including telmisartan. In addition, orthostatic hypotension may increase with alcohol, barbiturates, drugs, or antidepressants. Corticosteroids (for systemic use) Corticosteroids weaken the effect of telmisartan. Storage conditions The product should be stored out of the reach of children at a temperature not exceeding 25 ° C Term hodnosty 2 years active substance Telmisartan Terms leave through pharmacies In retseptu
