Telmisartan-Teva 80 mg tablets # 28

Telmisartan-Teva instructions for use

Composition

active ingredient: telmisartan; 1 tablet contains telmisartan 80 mg;
auxiliary substances: sodium hydroxide, hypromellose, sorbitol (E 420), povidone, meglumine, mannitol (E 421), magnesium stearate.

Dosage form

Pills.

Pharmacological group

Simple preparations of angiotensin II antagonists. The code of automatic telephone exchange С09С А07.

Indications

Hypertension.

Treatment of essential hypertension in adults.

Prevention of cardiovascular diseases.

Reduction in the incidence of cardiovascular disease in patients with:

• marked manifestations of atherothrombotic cardiovascular disease (coronary heart disease, stroke or peripheral arterial disease in history);
• diabetes mellitus type II with a diagnosed lesion of target organs.

Contraindications

Hypersensitivity to the active ingredient or to any of the excipients of the drug.

Pregnant women or women planning to become pregnant (see Application during pregnancy or lactation).

Obstructive diseases of the bile duct.

Severe liver dysfunction.

Age to 18 years.

Contraindicated simultaneous use of telmisartan and aliskirenvmisnih drugs in patients with diabetes mellitus or renal dysfunction (GFR <60 ml / min / 1.73 m 2) (see Sections "Interaction with other drugs and other interactions" and "Pharmacological properties"), .

Dosing and Administration

Telmisartan-Teva should be applied 1 time per day inward with a sufficient amount of liquid, regardless of food intake.

Treatment of arterial hypertension.

The recommended dose is 40 mg per day. For some patients, a dose of 20 mg per day is sufficient. If the level of blood pressure does not decrease to the desired figures, then you can increase the dose to a maximum of 80 mg once a day.Telmisartan-Teva can be administered in combination with thiazide diuretics hydrochlorothiazide, which have the additional effect of lowering blood pressure when administered along with telmisartan. When deciding whether to increase the dose, it should be borne in mind that the maximum hypotensive effect occurs after 4-8 weeks from the start of treatment.

Prevention of cardiovascular diseases.

The recommended dose is 80 mg once a day. It is not known whether a dose of telmisartan less than 80 mg is effective in reducing the level of cardiovascular morbidity.

At the beginning of treatment with telmisartan, careful monitoring of blood pressure is recommended to reduce the risk of cardiovascular disease. There may be a need for appropriate adjustment of the regimens for the use of drugs that lower blood pressure.

Impaired renal function.

In patients with mild or moderate renal insufficiency, there is no need for dose adjustment. There is limited experience in patients with renal insufficiency or hemodialysis. For these patients, a low initial dose of 20 mg is recommended.

Violation of the function of the liver.

For patients with impaired liver function of mild to moderate, the dose should not exceed 40 mg per day. Patients with severe violations of the liver drug is contraindicated.

Patients of advanced age.

Correction of the dose is not required.

Adverse Reactions

Serious side effects, including anaphylactic reactions and angioedema, are possible in some cases, acute renal failure was also observed.

Infectious diseases and infestations: infectious diseases of the upper respiratory tract (including pharyngitis and sinusitis), infectious diseases of the urinary tract (including cystitis), sepsis, including those with a lethal outcome ¹ .

On the part of the blood system and lymphatic system: anemia, thrombocytopenia, eosinophilia.

On the part of the immune system: hypersensitivity, anaphylactic reactions.

Metabolic disorders: hyperkalemia, hypoglycemia (in patients with diabetes mellitus).

Mental disorders: depression, insomnia, anxiety.

Neurological disorders: fainting, drowsiness.

From the side of the organ of vision: visual impairment.

From the organs of hearing and the vestibular apparatus: vertigo.

From the cardiovascular system: bradycardia, tachycardia, arterial hypotension ² , orthostatic hypotension.

From the respiratory system, chest and mediastinum: shortness of breath, cough, interstitial lung disease.

Cases of interstitial lung disease were observed temporarily when telmisartan was used during postmarketing observations. However, the causal relationship was not established.

From the gastrointestinal tract: abdominal pain, diarrhea, dyspepsia, flatulence, vomiting, stomach discomfort, dry mouth, dysgeusia.

Digestive system disorders: impaired liver function / liver function disorder. It was reported that patients of Japanese nationality are more prone to these adverse reactions.

From the skin and subcutaneous tissue: hyperhidrosis, pruritus, rash, erythema, angioedema (including fatal outcome), drug dermatitis, toxic dermatitis, eczema, urticaria.

From the musculoskeletal system and connective tissue: myalgia, back pain (for example, sciatica), muscle cramps, arthralgia, pain in the limbs, pain in the tendons (tendinitis symptoms).

From the side of the urinary system: a violation of kidney function, including acute renal failure.

Common disorders: chest pain, asthenia (weakness), flu-like symptoms.

Laboratory indicators: increase in the level of creatinine in the blood, increased levels of uric acid in the blood, increased levels of hepatic enzymes, increased levels of CK in the blood, a decrease in hemoglobin.

Description of individual adverse reactions

Sepsis. It was reported that patients taking telmisartan had a high incidence of sepsis than among those who received a placebo. This can be both an accident and a sign of a process, the essence of which is still unknown.

Hypotension. This adverse reaction was observed frequently in patients with controlled BP who were treated with telmisartan to reduce cardiovascular disease in addition to standard therapy.

Violation of liver function / hepatic disorders. According to post-marketing data, the majority of cases of liver function disorders / hepatic disorders were observed in patients of Japanese nationality. Patients of Japanese nationality are more prone to these adverse reactions.

Interstitial lung disease. Cases of interstitial lung disease were observed temporarily when telmisartan was used during postmarketing observations. However, the causal relationship was not established.

^{1 An} increase in the incidence of sepsis in the treatment of telmisartan compared with that of placebo was reported. This phenomenon can be an accidental manifestation or associated with a mechanism whose action is currently unknown.

² Reported as frequent in patients with controlled BP treated with telmisartan to reduce cardiovascular morbidity in addition to standard therapy.

Overdose

Information on the overdose of telmisartan is limited.

The most pronounced symptoms of an overdose of telmisartan were arterial hypotension and tachycardia also reported on bradycardia, dizziness, increased serum creatinine, and acute renal failure.

Telmisartan is not removed from the body by hemodialysis. The patient should be carefully monitored and symptomatic and supportive therapy is necessary. Treatment depends on the time that has passed since the overdose, and the severity of the symptoms. It is recommended to induce vomiting and / or rinse the stomach. In the treatment of overdose, it is possible to use activated carbon. Frequent monitoring of serum electrolytes and creatinine levels should be carried out. If arterial hypotension occurs, the patient should be given a supine position and restoring the balance of fluid and salt in the body.

Use during pregnancy and lactation

Pregnancy.

The drug is contraindicated for pregnant women or women planning pregnancy. If during pregnancy the pregnancy is confirmed, its use should be stopped immediately and, if necessary, replaced with another drug approved for use in pregnant women.

There is insufficient data on the use of telmisartan in pregnant women.

The epidemiological basis for the risk of teratogenicity resulting from the use of ACE inhibitors during the first trimester of pregnancy was not convincing, but a small increase in risk can not be ruled out. Although there are no controlled epidemiological data on the risk of teratogenicity in the use of angiotensin II receptor antagonists, such risks may exist for this class of drugs. When planning pregnancy, it is necessary to replace the drug in advance with another antihypertensive drug that has an established safety profile for use during pregnancy. When pregnancy is established, treatment with angiotensin II receptor antagonists should be stopped immediately and, if necessary, started with alternative treatment.

As is known, the use of angiotensin II receptor antagonists during the II and III trimesters of pregnancy causes fetotoxicity in humans (impaired renal function, oligohydramnios, delayed formation of the skull bones) and neonatal toxicity (kidney failure, hypotension, hyperkalemia). If the use of angiotensin II receptor antagonists began with the second trimester of pregnancy, it is recommended to perform an ultrasound examination of the kidneys and bones of the fetal skull. The state of newborns whose mothers have received angiotensin II receptor antagonists should be carefully monitored for arterial hypotension.

Breastfeeding.

Since there is no information on the use of telmisartan during breastfeeding, it is not recommended to use it and alternative therapies with established safety profiles during breastfeeding should be used, especially during the feeding of newborns or premature infants.

Fertility.

Pre-clinical studies have shown no effect of telmisartan on male and female fertility.

Children

The efficacy and safety of the drug in children under the age of 18 years have not been investigated.

Application features

Pregnancy.

During pregnancy, angiotensin II receptor antagonists should not be started. If continuation of therapy can not be considered extremely necessary for a patient who is planning a pregnancy, she should switch to alternative antihypertensive therapy, which has an established safety profile for use during pregnancy. When pregnancy is established, treatment with angiotensin II receptor antagonists should be stopped immediately and, if necessary, started with alternative treatment (see Sections "Contraindications" and "Use during pregnancy or lactation").

Liver failure.

Telmisartan-Teva should not be used in patients with cholestasis, obstructive diseases of the biliary system and severe hepatic insufficiency, since telmisartan is mainly excreted with bile. In patients with these diseases, the hepatic clearance of telmisartan is reduced. Caution should be exercised with Telmisartan-Teva in patients with mild to moderate hepatic impairment.

Renovascular hypertension.

There is a risk of severe arterial hypotension and renal failure in patients with bilateral renal artery stenosis or stenosis of the renal artery of a single kidney when treated with drugs that affect the renin-angiotensin-aldosterone system.

Renal failure and kidney transplantation.

When applying the drug to patients with impaired renal function, it is recommended to periodically monitor the level of potassium and creatinine in the blood serum. The experience of applying the drug to patients after kidney transplantation is not present.

Decrease of BCC.

Symptomatic arterial hypotension, especially after the first dose of the drug, may occur in patients with a reduced volume of circulating blood or hyponatremia, which are due to intensive diuretic therapy, diets with restriction of salt or diarrhea and vomiting. Such conditions should be adjusted before use. Before the start of treatment, it is necessary to normalize the sodium level and the volume of intravascular fluid.

Double blockade of renin-angiotensin-.

There is evidence that simultaneous use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren increases the risk of hypotension, hyperkalemia and reduces renal function (including acute renal failure).

Therefore, the double blockade of renin-angiotensin-by the addition of an ACE inhibitor to the angiotensin II receptor antagonist) is not recommended. If a double blockade is considered absolutely necessary, it should only be performed under the supervision of a specialist and under the condition of constant careful monitoring of kidney function, electrolytes and blood pressure.

ACE inhibitors and angiotensin II receptor blockers should not be used concurrently in patients with diabetic nephropathy.

Other conditions, accompanied by stimulation of renin-angiotensin-.

In patients whose vascular tone and kidney function are largely dependent on the activity of renin-angiotensin (for example, in patients with severe congestive heart failure or severe kidney disease, including renal artery stenosis), treatment with drugs that also affect this system, can cause acute arterial hypotension, hyperazotemia, oliguria or, more rarely, acute renal failure.

Primary aldosteronism.

Usually patients with primary aldosteronism do not respond to antihypertensive drugs that suppress the renin-angiotensin system, therefore it is not recommended to appoint telmisartan to patients with this condition.

Stenosis of mitral and aortic valves, obstructive hypertrophic cardiomyopathy.

As with the use of other vasodilators, caution should be given to patients with mitral and aortic stenosis or obstructive hypertrophic cardiomyopathy.

Hyperkalemia.

The use of drugs that affect renin-angiotensin-aldosterone can cause hyperkalemia.

In elderly patients, in patients with renal insufficiency, patients with diabetes, in patients who simultaneously receive other drugs that can increase the level of potassium and / or in patients with intercurrent diseases, hyperkalemia can lead to death.

Before the simultaneous use of drugs that suppress the renin-angiotensin-aldosterone system, the benefit / risk ratio should be assessed.

The main risk factors for hyperkalemia, which should be taken into account:

• diabetes mellitus, renal failure, age (> 70 years);
• combination with one or more drugs affecting the renin-angiotensin-aldosterone system, and / or with nutritional supplements containing potassium. Drugs or therapeutic classes of drugs that can provoke hyperkalemia include potassium-containing salt substitutes, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, non-steroidal anti-inflammatory drugs (NSAIDs, including selective COX-2 inhibitors), heparin, immunosuppressants (cyclosporin or tacrolimus) and trimethoprim;
• intercurrent manifestations, in particular, dehydration, acute cardiac decompensation, metabolic acidosis, impaired renal function, unexpected deterioration of the kidneys (infectious diseases), cell lysis (eg acute limb ischemia, rhabdomyolysis, severe trauma).

It is recommended that the potassium serum be monitored closely in patients at risk.

Sorbitol.

The drug contains sorbitol (E 420), so it should not be prescribed to patients with hereditary intolerance to fructose.

Ethnic differences.

As has been shown in the appointment of ACE inhibitors, telmisartan and other angiotensin receptor blockers are less effective in lowering blood pressure in patients of the Negroid race than in other races, perhaps because the level of renin in patients of the Negroid race with hypertension is less than in the representatives other races.

Others.

As with other antihypertensive agents, excessive blood pressure lowering in patients with coronary heart disease and ischemic cardiomyopathy can lead to myocardial infarction or stroke.

Diabetic patients who are treated with insulin or hypoglycemic drug.

Patients receiving insulin or antidiabetic drugs may have hypoglycemia. These patients need to control the level of glucose in the blood, and this should be taken into account in the correction dose of insulin or antidiabetic agents.

In patients with diabetes, cardiovascular risk (patients, patients with diabetes, with concomitant coronary artery disease), the risk of myocardial infarction deaths and sudden cardiovascular death may be higher in treatment with antihypertensive drugs such as receptor antagonists of angiotensin II, and ACE inhibitors. In patients with diabetes mellitus, coronary artery during concomitant diseases may be asymptomatic and therefore they can be undiagnosed. Patients with diabetes should be carefully evaluated, e.g., stress testing in order to detect and treat diseases associated coronary arteries before assign drug.

The ability to influence the reaction rate when driving vehicles or other mechanisms

In applying antihypertensive therapy can sometimes arise state of dizziness or drowsiness. So if you need to drive vehicles or work should take this into account with other mechanisms.

Interaction with other drugs and other interactions

Digoxin.

With simultaneous use of telmisartan and digoxin observed mean peak increase of digoxin concentrations in plasma (49%) and the lowest concentration (20%). At the beginning of the reception, in the case of correct dose and discontinuation of telmisartan should monitor digoxin levels to maintain them within the therapeutic range.

As with other drugs that affect the renin-angiotensin-aldosterone system, telmisartan may cause hyperkalemia. This risk may increase when combined with other drugs that may also induce hyperkalemia (potassium-containing salt substitutes, potassium-sparing diuretics, ACE inhibitors, angiotensin AI receptor antagonists, NSAIDs (including selective COX-2 inhibitors), heparin, immunosuppressive (cyclosporine or tacrolimus) and trimethoprim).

The incidence of hyperkalemia depends on associated risk factors. The risk increases with the use of therapeutic combinations mentioned above. This risk is especially high when combined with a potassium-sparing diuretic and salt substitute containing potassium. Combinations, such as ACE inhibitors or NSAIDs posing less risk under strict caution in use.

Simultaneous use is not recommended.

With potassium-sparing diuretics or food supplements containing potassium.

Antagonists of angiotensin AI receptor, such as telmisartan, reduce the loss of potassium that its cause diuretics. Potassium-sparing diuretics such as spironolactone, eplerenone, amiloride and triamterene, dietary supplements containing potassium or potassium-containing salt substitutes, may lead to a significant increase in potassium level in serum. If the result shows simultaneous application diagnosed hypokalemia, these drugs should be used with caution with frequent monitoring of serum potassium.

With lithium.

With simultaneous use of lithium with ACE inhibitors and angiotensin II receptor antagonists, including telmisartan mentioned reversible increases lithium concentration in the blood plasma and toxicity. If the application of this combination is necessary, it is recommended careful control of the level of lithium in serum.

Simultaneous application that requires caution.

Nonsteroidal anti-inflammatory drugs.

NSAIDs (e.g. acetylsalicylic acid in a dose intended for the treatment of inflammation, COX-2 inhibitors and the nonselective NSAIDs) may reduce the antihypertensive effect of angiotensin II receptor antagonists.

In some patients with impaired renal function (in patients with dehydration or elderly patients with impaired renal function) the simultaneous use of the angiotensin II receptor antagonists and of oppressive COX, may lead to further deterioration of renal function, including possible acute renal failure, which is usually It is reversible. Therefore, this combination should be used with caution, especially in elderly patients. Patients should receive adequate amount of liquid to be weighed and the possibility of kidney function after the start of control simultaneous treatment and periodically thereafter.

Reported increase is almost 2.5 times AUC 0-24 and C max while the use of ramipril and ramiprilat. The clinical relevance of this message is unknown.

Diuretics (thiazide or loop).

Pre-treatment with high doses of diuretics such as furosemide (loop diuretic) and hydrochlorothiazide (thiazide diuretic) may lead to dehydration and the risk of hypotension in the early treatment telmizartanom.

It should be taken into account while applying.

Other antihypertensive drugs.

Effect telmizartana - lowering blood pressure - can grow while the use of other antihypertensive drugs.

In view of the pharmacological properties it can be expected that such drugs as baclofen, amifostine, can cause hypotensive effects of antihypertensive agents including telmisartan. Also, orthostatic hypotension may deteriorate due to alcohol, barbiturates, narcotics or antidepressants.

Corticosteroids (systemic application).

Reduced antihypertensive effect.

Dual blockade of the renin-angiotensin.

It demonstrated that dual blockade of the renin-angiotensin (RAAS) by simultaneous application of ACE inhibitors, angiotensin II receptor antagonists or aliskiren is characterized by a higher frequency of adverse events as arterial hypotension, hyperglycemia, decreased renal function (including acute renal failure) as compared with using monotherapy.

Pharmacological properties

Pharmacodynamics.

Telmizartan is oral specific antagonist of angiotensin II receptor (type 1 AO). With high affinity telmisartan replaces angiotensin II in places with its binding species AO 1 receptors are mediated through the action of angiotensin II. Telmizartan does not exhibit any partial agonistic effect on AO 1 receptor.

Telmizartan selectively binds the AT1 receptor for a long time without even partial agonistic effect on it. Binding is long-lasting.

Telmizartan has no affinity to other receptors, including AO 2 receptor antibodies and other receptors. The functional role of these receptors have not been elucidated as their possible effect stimulation by angiotensin II, whose levels rise telmizartanom. Telmizartan reduced aldosterone levels in plasma, does not block the ion channels and does not reduce the level of renin in blood plasma. It does not lead to the inhibition of the ACE enzyme (kininazy II), an enzyme that degrades bradykinin also. Therefore, it is expected side effects mediated by bradykinin.

In humans, the dose of 80 mg telmizartana almost completely inhibits the angiotensin II-induced elevation of blood pressure. The inhibitory effect is maintained throughout the day and is determined up to 48 hours.

Pharmacokinetics.

Telmizartan rapidly absorbed, but the amount of drug absorbed, is not the same. Average bioavailability of telmisartan is approximately 50%.

When telmisartan with food decreases the area under the concentration / time curve (AUC) for telmizartana of 6% (40 mg dose) and 19% (160 mg dose). After 3:00 reception plasma concentration becomes the same as with telmisartan without food.

It is believed that a slight decrease in AUC does not reduce the therapeutic efficacy of the drug. There is a linear relationship between dose and plasma level. C max and AUC are less disproportionately increased at doses above 40 mg.

Telmizartan largely bound to plasma proteins (99.5%), mostly to albumin and alpha-1-acid glycoprotein. The mean volume of distribution (V ss) in the equilibrium state is approximately 500 liters.

Telmizartan metabolised by conjugation to glucuronide starting compound does not possess pharmacological activity.

Telmizartan characterized bieksponentsionalnoyu pharmacokinetic curve with a terminal half-life of more than 20 hours. The maximum plasma concentration (C max) and to a lesser extent the area under the curve "concentration / time" (AUC) increases disproportionately dose. When telmisartan at recommended doses clinically significant accumulation has been detected. plasma concentrations were higher in females than in males, without a corresponding effect on the efficiency.

After receiving (and intravenous) administration telmisartan almost completely excreted in feces mainly as unchanged.

The cumulative urinary excretion of less than 1% of the dose. Total plasma clearance (CL tot) is high (approximately 1000 ml / min) compared with the blood flow through the liver (approximately 1500 ml / min).

Specific categories of patients.

Children. The pharmacokinetics of two doses telmizartana was evaluated as a secondary objective for hypertensive patients (n = 57) aged 6 to <18 telmisartan after a dose of 1 mg / kg or 2 mg / kg for 4 weeks of treatment. Pharmacokinetic objectives included determining telmizartana levels in a stable condition in children and adolescents, and the study of differences related to age. Although the study was not sufficient for a reliable assessment of the pharmacokinetics in children aged up to 12 years, the results are broadly consistent with the data obtained for both adults and confirm telmizartana nonlinearity, in particular, to C max.

Floor. plasma concentration C max and AUC in women about 3 and 2 times, respectively, higher than in men.

Elderly patients. Pharmacokinetics telmizartana not different in elderly patients and younger than 65 years.

Patients with impaired renal function. In patients with mild to moderate and severe renal insufficiency, an increase in 2 times the plasma concentration. However, in patients with renal insufficiency patients subject to dialysis observed low plasma concentration. Telmizartan has a high affinity to plasma proteins in patients with renal failure and can not be removed by dialysis. In patients with renal insufficiency, the half-life is not changed.

Patients with impaired liver function. Pharmacokinetic studies in patients with impaired liver bioavailability found an increase of about 100%. In patients with hepatic failure half-life is not changed.

Basic physical and chemical properties

white or almost white oblong tablets with a fault line on one side.

Shelf life

3 years.

Storage conditions

The preparation does not require any special storage conditions. Keep out of the reach of children.

Packaging

7 tablets in a blister, with 4 blisters per box.

Category of leave

On prescription.