Description
Release form long white, slightly white or white firms are on the other side.
Pharmacological action
Clinical and pharmacological group: Angiotensin II receptor antagonist
Pharmacotherapeutic group: Angiotensin II receptor antagonist
Pharmacological action
Antihypertensive drug.
Pharmacodynamics
Telmisartan is a specific angiotensin II receptor antagonist. It has a high affinity for the AT1 receptor subtype of angiotensin II, through which the action of angiotensin II is realized. Telmisartan displaces angiotensin II from its binding to the receptor, lacking the action of an agonist in relation to this receptor. It forms a connection only with the AT1 receptor subtype of angiotensin II. Binding is continuous. Telmisartan Has No Affinity for Other Recetsfluorides (including AT2 receptors) 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. It reduces the concentration of aldosterone in the blood, does not inhibit renin in blood plasma and does not block ion channels. It does not inhibit ACE (kininase II), an enzyme that also destroys bradykinin, therefore, an increase in side effects caused by bradykinin is not expected.
Telmisartan at a dose of 80 mg completely blocks the hypertensive effect of angiotensin II. The onset of hypotensive action is noted within 3 hours after the first administration of telmisartan. The effect of the drug persists for 24 hours and remains significant up to 48 hours. A pronounced hypotensive effect usually develops after 4-8 weeks of regular use.
In patients with arterial hypertension, telmisartan reduces systolic and diastolic blood pressure without affecting heart rate.
In the case of abrupt cancellation of telmisartan, blood pressure gradually returns to its original level without the development of withdrawal syndrome.
Pharmacokinetics
Absorption
When taken orally, telmisartan is rapidly absorbed from the digestive tract. Bioavailability is 50%.
When taken concomitantly with food, the decrease in AUC values ranges from 6% (when used in a dose of 40 mg) to 19% (when used in a dose of 160 mg). 3 hours after ingestion, the concentration in the blood plasma is leveled regardless of the time of eating.
Distribution of
Binding to blood plasma proteins – more than 99.5%, mainly with albumin and 1-glycoprotein. The average value of the apparent Vd in equilibrium is 500 liters.
Metabolism
Metabolized by conjugation with glucuronic acid. Metabolites are not pharmacologically active.
Excretion
T1 / 2 – more than 20 hours. It is excreted through the intestine unchanged, excretion by the kidneys – less than 2% of the dose. The total plasma clearance is high (900 ml / min) compared with hepatic blood flow (about 1500 ml / min).
Pharmacokinetics in special clinical cases
There is a difference in concentrations between men and women. In women, Cmax and AUC were approximately 3 and 2 times respectively higher than in men (without a significant effect on effectiveness).
The pharmacokinetics of telmisartan in elderly patients are not different from the pharmacokinetics in young patients. Dose adjustment is not required.
Dose adjustment in patients with renal failure is not required, including patients on hemodialysis. Telmisartan is not removed by hemodialysis.
In patients with impaired liver function of mild to moderate degree (class A and B on the Child-Pugh scale), the daily dose should not exceed 40 mg.
The main indicators of the pharmacokinetics of telmisartan in children and adolescents aged 6 to 18 after taking telmisartan at a dose of 1 mg / kg or 2 mg / kg for 4 weeks are generally comparable with the data obtained in the treatment of adults and confirm the nonlinearity pharmacokinetics of telmisartan, especially with respect to Cmax.
Indications
– arterial hypertension
– reduction of cardiovascular morbidity and mortality in patients aged 55 years and older with a high risk of cardiovascular disease.
Contraindications
– obstructive biliary tract disease
– severe liver dysfunction (Child-Pugh class C)
– simultaneous use with aliskiren in patients with diabetes mellitus or renal failure (GFR <60 ml / s / ldp 1.73 m2) Fructose intolerance glucose / galactose malabsorption syndrome or sucrose / isomaltase deficiency – under 18 years of age (efficacy and safety not established) – pregnancy – breastfeeding period – hypersensitivity to the active substance or auxiliary components of the drug. With caution – bilateral renal artery stenosis or stenosis of a single kidney artery – impaired liver and / or kidney function – decrease in bcc due to previous diuretic therapy, restriction of salt intake, diarrhea or vomiting – hyponatremia – hyperkalemia – conditions after kidney transplantation (no experience with application) – chronic heart failure – stenosis of the aortic and mitral valve – idiopathic hypertrophic subaortal stenosis and primary safety ( ) – primary. Use during pregnancy and lactation The use of the drug Mikardis ® is contraindicated in pregnancy. The use of angiotensin II receptor antagonists in the first trimester of pregnancy is not recommended, these drugs should not be prescribed during pregnancy. When diagnosing pregnancy, the use of the drug should be stopped immediately. If necessary, alternative therapy should be prescribed (other classes of antihypertensive drugs approved for use during pregnancy). The use of angiotensin II receptor antagonists in the second and third trimesters of pregnancy is contraindicated. In preclinical studies of telmisartan, teratogenic effects were not detected, but fetotoxicity was established. It is known that the effects of angiotensin II receptor antagonists in the II and III trimesters of pregnancy cause fetotoxicity in a person (decreased renal function, oligohydramnios, delayed ossification of the skull), as well as neonatal toxicity (renal failure, hypotension, hyperkalemia). Patients those planning a pregnancy should be prescribed alternative therapy. If treatment with angiotensin II receptor antagonists was carried out in the II trimester of pregnancy, ultrasound of the kidneys and skull bones of the fetus is recommended. Newborns whose mothers received angiotensin II receptor antagonists should be closely monitored for arterial hypotension. Therapy with Mikardis ® is contraindicated during breastfeeding. Studies on the effects on human fertility have not been conducted. Special instructions In some patients, renal function (including acute renal failure) is impaired due to the suppression of RAAS, especially when using a combination of agents acting on this system. Therefore, therapy accompanied by a similar double blockade of RAAS (for example, with the addition of ACE inhibitors or a direct renin inhibitor, aliskiren, to angiotensin II receptor antagonist blockers), should be carried out strictly individually and with careful monitoring of renal function (including periodic monitoring of potassium concentration and serum creatinine). 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. Based on the experience of using other drugs that affect RAAS, while prescribing Mikardis ® and potassium-sparing diuretics, potassium-containing supplements, potassium-containing edible salt, and other drugs that increase the concentration of potassium in the blood (for example, heparin), this indicator should be monitored in patients. In patients with diabetes mellitus and additional cardiovascular risk, for example, in patients with diabetes mellitus and coronary heart disease, the use of drugs that reduce blood pressure, such as angiotensin II receptor antagonists or ACE inhibitors, may increase the risk of fatal myocardial infarction and sudden cardiac -vascular death. In patients with diabetes, coronary heart disease can be asymptomatic and therefore may be undiagnosed. Before starting the use of the drug Mikardis ® for the detection and treatment of coronary heart disease, appropriate diagnostic studies should be carried out, including test with physical activity. Alternatively, Mikardis ® can be used in combination with thiazide diuretics, such as hydrochlorothiazide, which additionally have a hypotensive effect (for example, Mikardis ® Plus 40 mg / 12.5 mg, 80 mg / 12.5 mg). In patients with primary aldosteronism, antihypertensive drugs whose mechanism of action is to inhibit RAAS are generally not effective. Caution must be exercised when using the drug Mikardis ® (as well as other vasodilators) in patients with aortic or mitral stenosis and with hypertrophic obstructive cardiomyopathy. Telmisartan is excreted mainly with bile. In patients with obstructive biliary tract disease or liver failure, a decrease in clearance of the drug can be expected. In patients with severe arterial hypertension, a dose of telmisartan of 160 mg / day in combination with hydrochlorothiazide 12.5-25 mg was effective and well tolerated. Dysfunction of the liver with the appointment of telmisartan in most cases was observed in residents of Japan. Mikardis ® is less effective in patients of the Negroid race. Influence on the ability to drive vehicles and control mechanisms Special clinical studies of the effect of the drug on the ability to drive a car and mechanisms have not been conducted. However, when driving and working with mechanisms, the possibility of developing dizziness and drowsiness should be taken into account, which requires caution. Composition 1 tab. telmisartan 40 mg Excipients: sodium hydroxide, polyvidone (collidone 25), meglumine, sorbitol, magnesium stearate. Dosage and administration The drug is administered orally, regardless of food intake. For arterial hypertension, the recommended starting dose of Mikardis® is 1 tab. (40 mg) 1 time / day. In cases where the therapeutic effect is not achieved, the dose of the drug can be increased to 80 mg 1 time / day. When deciding whether to increase the dose, it should be taken into account that the maximum antihypertensive effect is usually achieved within 4-8 weeks after the start of treatment. To reduce cardiovascular morbidity and mortality, the recommended dose is 1 tab. (80 mg) 1 time / day. In the initial period of treatment, additional correction of blood pressure may be required. Patients with renal failure (including those on hemodialysis) do not require dose adjustment. In patients with impaired liver function of mild to moderate degree (class A and B on the Child-Pugh scale), the daily dose should not exceed 40 mg. Dosage regimen in elderly patients does not require changes. Side effects Observed cases of side effects did not correlate with the gender, age or race of the patients. Infections: sepsis, including fatal sepsis, urinary tract infections (including cystitis), upper respiratory tract infections. From the hemopoietic system: anemia, eosinophilia, thrombocytopenia. From the side of the central nervous system: insomnia, anxiety, depression, fainting, vertigo. From the side of the organ of vision: visual disturbances. From the cardiovascular system: marked decrease in blood pressure, orthostatic hypotension, bradycardia, tachycardia. From the respiratory system: shortness of breath. From the digestive system: abdominal pain, diarrhea, dry mouth, dyspepsia, flatulence, discomfort in the stomach, vomiting, impaired liver function / liver disease * (* based on post-marketing observations, in most cases, impaired liver function / liver disease have been identified in Japanese patients). Allergic reactions: anaphylactic reactions, hypersensitivity (erythema, urticaria, angioedema), eczema, skin itching, rash (including drug), angioedema (fatal), toxic rash, hyperhidrosis. From the musculoskeletal system: arthralgia, back pain, muscle spasms (cramps of the calf muscles), pain in the lower extremities, myalgia, pain in the tendons (symptoms similar to the manifestation of tendonitis). From the urinary system: impaired renal function (including acute renal failure). On the part of laboratory indicators: a decrease in hemoglobin, an increase in the concentration of uric acid and creatinine in the blood, an increase in the activity of liver enzymes, an increase in CPK activity, hyperkalemia, hypoglycemia (in patients with diabetes mellitus). Other: chest pain, flu-like syndrome, general weakness. Drug Interactions Telmisartan may increase the hypotensive effect of other antihypertensive drugs. Other types of interaction with clinical significance have not been identified. Combined use with digoxin, warfarin, hydrochlorothiazide, glibenclamide, ibuprofen, paracetamol, simvastatin and amlodipine does not lead to a clinically significant interaction. A marked increase in the average concentration of digoxin in blood plasma by an average of 20% (in one case, by 39%). With the simultaneous administration of telmisartan and digoxin, it is advisable to periodically determine the concentration of digoxin in the blood. With the simultaneous use of telmisartan and ramipril, a 2.5-fold increase in AUC0-24 and Cmax of ramipril and ramipril was observed. The clinical significance of this phenomenon has not been established. With the simultaneous use of ACE inhibitors and lithium preparations, a reversible increase in the concentration of lithium in the blood was observed, accompanied by a toxic effect. In rare cases, such changes have been reported with the appointment of angiotensin II receptor antagonists. With the simultaneous administration of lithium preparations and angiotensin II receptor antagonists, it is recommended to determine the concentration of lithium in the blood. Treatment of NSAIDs, including acetylsalicylic acid, COX-2 inhibitors and non-selective NSAIDs, may cause the development of acute renal failure in patients with dehydration. Drugs acting on RAAS may have a synergistic effect. In patients receiving NSAIDs and telmisartan, bcc should be compensated at the beginning of treatment and a kidney function test should be performed. A decrease in the effect of antihypertensive agents such as telmisartan by inhibiting the vasodilating effect of prostaglandins has been observed with concomitant therapy with NSAIDs. Overdose No cases of overdose. Symptoms: marked decrease in blood pressure, tachycardia, bradycardia. Treatment: symptomatic treatment. Hemodialysis is ineffective. Storage conditions The product should be stored out of the reach of children, protected from moisture, at a temperature not exceeding 30 ° C. Expiration 4 years. active substance Telmisartan Terms leave through pharmacies In retseptu lekarstvennaja form tablets Beringer Ingelyhaym, Austria
