Telmista, tablets 80 mg 28 pcs

Hypertension (high blood pressure)

Essential hypertension.

Reduction in mortality and cardiovascular events in adult patients:

– with cardiovascular diseases of atherothrombotic genesis (coronary heart disease, stroke or peripheral artery disease in the anamnesis);

– with type 2 diabetes mellitus with target organ damage.

Indications

Essential hypertension.

Reducing mortality and incidence of cardiovascular diseases in adult patients:

– with cardiovascular diseases of atherothrombotic origin (coronary heart disease, stroke or history of peripheral artery disease);

– with type 2 diabetes mellitus with target organ damage.

Pharmacological effect

angiotensin II receptor antagonist (ARA II)

Special instructions

Bilateral renal artery stenosis or stenosis of the artery of a single kidney.

Impaired liver and/or kidney function (see section “Special instructions”).

A decrease in circulating blood volume (CBV) due to previous diuretic therapy, restriction of salt intake, diarrhea or vomiting.

Hyponatremia.

Hyperkalemia.

Conditions after kidney transplantation (no experience with use).

Chronic heart failure (CHF).

Stenosis of the aortic and/or mitral valve.

Hypertrophic obstructive cardiomyopathy (HOCM).

Primary hyperaldosteronism (efficacy and safety have not been established).

Use in patients of the Negroid race.

The use of the drug in children and adolescents under 18 years of age is contraindicated due to the lack of data on safety and effectiveness.

Renal dysfunction

Experience with the use of telmisartan in patients with severe renal impairment or patients on hemodialysis is limited.

A lower initial dose of 20 mg per day is recommended for these patients (see section “Special Instructions”). For patients with mild or moderate renal impairment, no dose adjustment is required.

The simultaneous use of Telmista® with drugs containing aliskiren in patients with diabetes mellitus and/or moderate to severe renal impairment (GFR less than 60 ml/min/1.73 m2 body surface area) is contraindicated (see section “Contraindications”).

The simultaneous use of Telmista® with ACE inhibitors is contraindicated in patients with diabetic nephropathy (see section “Contraindications”).

Liver dysfunction

Telmista® is contraindicated in patients with severe hepatic impairment (Child-Pugh class C) (see section “Contraindications”). In patients with mild to moderate hepatic impairment (Child-Pugh classes A and B, respectively), Telmista® is prescribed with caution; the dose should not exceed 40 mg once daily (see section “With caution”).

Elderly patients

For elderly patients, no dose adjustment is required.

Liver dysfunction

The use of Telmisartan is contraindicated in patients with cholestasis, biliary obstruction or severe liver dysfunction (Child-Pugh class C) (see section “Contraindications”), since telmisartan is mainly excreted in the bile. It is assumed that in such patients the hepatic clearance of telmisartan is reduced. In patients with mild or moderate hepatic impairment (Child-Pugh classes A and B), Telmista should be used with caution (see section “With caution”).

Renovascular hypertension

When treated with drugs that act on the RAAS, the risk of severe arterial hypotension and renal failure increases in patients with bilateral renal artery stenosis or arterial stenosis of a single functioning kidney.

Renal dysfunction and kidney transplantation

When using Telmista® in patients with impaired renal function, periodic monitoring of potassium levels and creatinine concentrations in blood plasma is recommended. There is no clinical experience with the use of telmisartan in patients who have recently undergone kidney transplantation.

Decrease in BCC

Symptomatic arterial hypotension, especially after the first dose of Telmista®, may occur in patients with low blood volume and/or sodium content in the blood plasma due to previous treatment with diuretics, restriction of salt intake, diarrhea or vomiting. Such conditions (hypovolemia and hyponatremia) must be eliminated before taking Telmista®.

Double blockade of the RAAS

The simultaneous use of telmisartan with drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or with moderate or severe renal impairment (GFR less than 60 ml/min/1.73 m2 body surface area) and is not recommended in other patients.

The simultaneous use of telmisartan and ACE inhibitors is contraindicated in patients with diabetic nephropathy (see section “Contraindications”) and is not recommended in other patients.

As a result of inhibition of the RAAS, the following have been observed: arterial hypotension, syncope, hyperkalemia and impaired renal function (including acute renal failure) in predisposed patients, especially with the simultaneous use of several drugs that also act on this system. Therefore, double blockade of the RAAS (for example, while taking telmisartan with other RAAS antagonists) is not recommended.

In cases where vascular tone and renal function depend primarily on the activity of the RAAS (for example, in patients with CHF or kidney diseases, including renal artery stenosis or stenosis of the artery of a single kidney), the prescription of 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 that act by inhibiting the RAAS is usually ineffective. In this regard, the use of Telmista® is not recommended.

Aortic or mitral valve stenosis, HOCM

As with other vasodilators, patients with aortic or mitral stenosis, as well as HOCM, must be especially careful when using Telmista®.

Patients with diabetes mellitus receiving insulin or oral hypoglycemic agents

During treatment with Telmista®, these patients may develop hypoglycemia. In such patients, glycemic control should be strengthened, as it may be necessary to adjust the dose of insulin or hypoglycemic agent.

Hyperkalemia

Taking medications that act on the RAAS can cause hyperkalemia. In elderly patients, patients with renal failure or diabetes mellitus, patients also taking medications that increase plasma potassium levels, and/or patients with underlying medical conditions, hyperkalemia can be fatal.

When deciding on the concomitant use of drugs acting on the RAAS, it is necessary to assess the risk-benefit ratio. The main risk factors for hyperkalemia that should be considered are:

diabetes mellitus, renal failure, age (patients over 70 years old);

simultaneous use with one or more drugs acting on the RAAS and/or potassium-containing nutritional supplements. Drugs or therapeutic classes of drugs that can cause hyperkalemia include potassium-containing salt substitutes, potassium-sparing diuretics, ACE inhibitors, ARB II, NSAIDs including selective COX-2 inhibitors, heparin, immunosuppressants (cyclosporine or tacrolimus) and trimethoprim;

intercurrent diseases, especially dehydration, acute heart failure, metabolic acidosis, renal dysfunction, cytolysis syndrome (for example, acute limb ischemia, rhabdomyolysis, major trauma).

Patients at risk are advised to carefully monitor the potassium content in the blood plasma (see section “Interaction with other drugs”).

Ethnic differences

As noted for ACE inhibitors, telmisartan and other APA IIs appear to be less effective in lowering blood pressure in black patients than in other races, possibly due to a greater predisposition to decreased renin activity in these patient populations.

Other

As with the use of other antihypertensive drugs, a pronounced decrease in blood pressure in patients with ischemic cardiomyopathy or coronary artery disease can lead to the development of myocardial infarction or stroke.

Special information on excipients

For patients with rare hereditary fructose or lactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome, Telmista® is contraindicated because it contains lactose and sorbitol (E420).

No special clinical studies have been conducted to study the effect of the drug on the ability to drive a car or use machinery. When driving vehicles and working with mechanisms that require increased concentration, caution should be exercised, since dizziness and drowsiness may rarely occur while taking Telmista®.

Active ingredient

Telmisartan

Composition

1 tablet 40 mg/80 mg contains:

Active ingredient:

Telmisartan 40.00 mg/80.00 mg

Excipients:

Meglumine, sodium hydroxide, povidone-K30, lactose monohydrate, sorbitol (E420), magnesium stearate

Pregnancy

Pregnancy

The use of Telmista® is contraindicated during pregnancy. The use of ARA II in the first trimester of pregnancy is not recommended; these drugs should not be used during pregnancy. If pregnancy is diagnosed, taking Telmista® should be stopped immediately. If necessary, alternative antihypertensive therapy (other classes of antihypertensive drugs approved for use during pregnancy) should be prescribed.

The use of ARA II in the second and third trimesters of pregnancy is contraindicated.

In preclinical studies of telmisartan, no teratogenic effects were identified, but fetotoxicity was established. It is known that the use of ARA II in the second and third trimesters of pregnancy causes fetotoxicity in humans (decreased renal function, oligohydramnios, delayed ossification of fetal skull bones), as well as neonatal toxicity (renal failure, arterial hypotension, hyperkalemia). Patients planning pregnancy should use alternative therapy. If, nevertheless, ARA II was used in the second or third trimesters of pregnancy, then it is necessary to conduct an ultrasound examination of the kidneys and bones of the fetal skull.

Newborns whose mothers took ARA II during pregnancy should be monitored, as arterial hypotension may develop in the newborn.

Breastfeeding period

There is no information on the use of telmisartan during breastfeeding. Taking Telmista® during breastfeeding is contraindicated (see section “Contraindications”), an alternative antihypertensive drug with a more favorable safety profile should be used, especially when feeding a newborn or premature baby.

No studies have been conducted to examine the effect on human fertility.

Contraindications

Hypersensitivity to the active substance or excipients of the drug.

Pregnancy.

Breastfeeding period.

Obstructive diseases of the biliary tract.

Severe liver dysfunction (class C according to the Child-Pugh classification).

Concomitant use with aliskiren and drugs containing aliskiren in patients with diabetes mellitus and/or moderate to severe renal impairment (glomerular filtration rate [GFR] less than 60 ml/min/1.73 m2 body surface area).

Concomitant use with ACE inhibitors in patients with diabetic nephropathy.

Fructose or lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome (Telmista® contains lactose and sorbitol [E420]).

Age up to 18 years (efficacy and safety have not been established).

Side Effects

According to the World Health Organization (WHO), adverse effects are classified according to the frequency of their development as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), frequency unknown - based on available data, it was not possible to determine the frequency of occurrence.

Within each group, according to frequency of occurrence, adverse reactions are presented in descending order of severity.

Infectious and parasitic diseases

uncommon: urinary tract infections, including cystitis, upper respiratory tract infections, including pharyngitis and sinusitis;

rarely: sepsis, including death.

Blood and lymphatic system disorders

uncommon: anemia;

rarely: eosinophilia, thrombocytopenia.

Immune system disorders

rarely: anaphylactic reaction, hypersensitivity.

Metabolic and nutritional disorders

uncommon: hyperkalemia;

rarely: hypoglycemia (in patients with diabetes mellitus).

Mental disorders

uncommon: insomnia, depression;

rarely: anxiety.

Nervous system disorders

uncommon: fainting;

rarely: drowsiness.

Visual disorders

rarely: visual disturbances.

Hearing and labyrinth disorders

uncommon: vertigo.

Heart disorders

uncommon: bradycardia;

rarely: tachycardia.

Vascular disorders

uncommon: marked decrease in blood pressure, orthostatic hypotension.

Respiratory, thoracic and mediastinal disorders

uncommon: shortness of breath, cough;

very rare: interstitial lung disease.

Gastrointestinal disorders

uncommon: abdominal pain, diarrhea, dyspepsia, flatulence, vomiting;

rarely: dryness of the oral mucosa, discomfort in the stomach, disturbance of taste.

Disorders of the liver and biliary tract

rarely: liver dysfunction/liver damage.

Skin and subcutaneous tissue disorders

uncommon: skin itching, hyperhidrosis, skin rash;

rare: angioedema (also fatal), eczema, erythema, urticaria, drug rash, toxic skin rash.

Musculoskeletal and connective tissue disorders

uncommon: back pain (sciatica), muscle spasms, myalgia;

rarely: arthralgia, pain in the limbs, pain in the tendons (tendinitis-like syndrome).

Renal and urinary tract disorders

uncommon: renal dysfunction, including acute renal failure.

General and administration site disorders

uncommon: chest pain, asthenia (weakness);

rarely: influenza-like syndrome.

Laboratory and instrumental studies

uncommon: increased plasma creatinine concentration;

rarely: decreased hemoglobin, increased concentration of uric acid in the blood plasma, increased activity of liver enzymes and creatine phosphokinase (CPK) in the blood plasma.

Interaction

Dual blockade of the renin-angiotensin-aldosterone system (RAAS)

The simultaneous use of telmisartan with drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or with moderate or severe renal impairment (GFR less than 60 ml/min/1.73 m2 body surface area) and is not recommended in other patients.

The simultaneous use of telmisartan and ACE inhibitors is contraindicated in patients with diabetic nephropathy (see section “Contraindications”) and is not recommended in other patients.

Data from clinical studies have shown that dual blockade of the RAAS due to the combined use of ACE inhibitors, APA II or aliskiren is associated with an increased incidence of adverse events such as hypotension, hyperkalemia and renal dysfunction (including acute renal failure) compared with the use of only one drug acting on the RAAS.

The risk of developing hyperkalemia may be increased when used concomitantly with other drugs that can cause hyperkalemia (potassium-containing dietary supplements and potassium-containing salt substitutes, potassium-sparing diuretics [eg, spironolactone, eplerenone, triamterene, or amiloride], nonsteroidal anti-inflammatory drugs [NSAIDs], including selective cyclooxygenase-2 (COX-2) inhibitors), heparin, immunosuppressants [cyclosporine or tacrolimus], and trimethoprim). If necessary, against the background of documented hypokalemia, simultaneous use of drugs should be carried out with caution and regular monitoring of potassium levels in the blood plasma.

Digoxin

With simultaneous use of telmisartan with digoxin, an average increase in Cmax of digoxin in blood plasma by 49% and minimum concentration by 20% was noted. At the beginning of treatment, when selecting a dose and stopping treatment with telmisartan, the concentration of digoxin in the blood plasma should be carefully monitored to maintain it within the therapeutic range.

Potassium-sparing diuretics or potassium supplements

II ARBs, such as telmisartan, reduce diuretic-induced potassium loss. Potassium-sparing diuretics, such as spironolactone, eplerenone, triamterene or amiloride, potassium-containing dietary supplements or salt substitutes may lead to a significant increase in plasma potassium levels. If concomitant use is indicated because hypokalemia is documented, they should be used with caution and in conjunction with regular monitoring of plasma potassium levels.

Lithium preparations

With simultaneous use of lithium preparations with ACE and APA II inhibitors, including telmisartan, a reversible increase in the concentration of lithium in the blood plasma and its toxic effect occurred. If it is necessary to use this combination of drugs, it is recommended to carefully monitor lithium concentrations in the blood plasma.

NSAIDs

NSAIDs (i.e., acetylsalicylic acid at doses used for anti-inflammatory treatment, COX-2 inhibitors and non-selective NSAIDs) may reduce the antihypertensive effect of APA II. In some patients with impaired renal function (eg, dehydrated patients, elderly patients with impaired renal function), concomitant use of APA II and drugs that inhibit COX-2 may lead to a further deterioration of renal function, including the development of acute renal failure, which is usually reversible. Therefore, the simultaneous use of drugs should be carried out with caution, especially in elderly patients. Adequate fluid intake should be ensured and renal function should be monitored at the start of co-administration and periodically thereafter.

Diuretics (thiazide or loop)

Previous treatment with high doses of diuretics such as furosemide (loop diuretic) and hydrochlorothiazide (thiazide diuretic) may lead to hypovolemia and the risk of hypotension when starting treatment with telmisartan.

Other antihypertensive drugs

The effect of telmisartan may be enhanced by simultaneous 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 be exacerbated by the use of alcohol, barbiturates, narcotics, or antidepressants.

Corticosteroids (for systemic use)

Corticosteroids weaken the effect of telmisartan.

Overdose

Symptoms: The most pronounced manifestations of overdose were a marked decrease in blood pressure and tachycardia, and bradycardia, dizziness, increased serum creatinine concentrations and acute renal failure were also reported.

Treatment: telmisartan is not eliminated by hemodialysis. Patients should be carefully monitored and treated symptomatically as well as supportively. The treatment approach depends on the time elapsed after taking the drug and the severity of symptoms. Recommended measures include inducing vomiting and/or gastric lavage; it is advisable to take activated charcoal. Electrolyte levels and plasma creatinine concentrations should be regularly monitored. If a pronounced decrease in blood pressure occurs, the patient should take a horizontal position with his legs elevated, and it is necessary to quickly replenish the volume of blood volume and the content of electrolytes.

Clinical pharmacology

Pharmacodynamics

Telmisartan is a specific ARA II (type AT1), effective when taken orally. It has a high affinity for the AT1 subtype of angiotensin II receptors, through which the action of angiotensin II is realized. Displaces angiotensin II from its connection with the receptor, without having an agonist effect on this receptor. Telmisartan binds only to the AT1 subtype of angiotensin II receptors. The connection is long-term. It has no affinity for other receptors, 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 by angiotensin II, the concentration of which increases with the use of telmisartan, have not been studied. Reduces the concentration of aldosterone in the blood plasma, does not inhibit renin in the blood plasma and does not block ion channels. Telmisartan does not inhibit angiotensin-converting enzyme (ACE) (kininase II) (an enzyme that also breaks down bradykinin). This avoids side effects associated with bradykinin (for example, dry cough).

Essential hypertension

In patients, telmisartan at a dose of 80 mg completely blocks the hypertensive effect of angiotensin II. The onset of antihypertensive action is observed within 3 hours after the first dose of telmisartan. The effect of the drug lasts for 24 hours and remains significant for up to 48 hours. A pronounced antihypertensive effect usually develops after 4-8 weeks of regular use of telmisartan.

In patients with arterial hypertension, telmisartan reduces systolic and diastolic blood pressure (BP) without affecting heart rate (HR).

In case of abrupt withdrawal of telmisartan, blood pressure gradually returns to the initial level without the development of 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 the use of telmisartan as opposed to ACE inhibitors.

Prevention of cardiovascular diseases

In patients aged 55 years or older with a history of coronary artery disease (CAD), stroke, transient ischemic attack, peripheral arterial disease, or complications of type 2 diabetes mellitus (eg, retinopathy, left ventricular hypertrophy, macro- or microalbuminuria) at risk for cardiovascular events, telmisartan had an effect similar to that of ramipril in reducing the composite endpoint: cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke and hospitalization due to chronic heart failure (CHF).

Telmisartan was as effective as ramipril in reducing the incidence of secondary endpoints: cardiovascular mortality and non-fatal myocardial infarction.

Dry cough and angioedema were less frequently described with telmisartan compared with ramipril, while arterial hypotension occurred more frequently with telmisartan.

Patients of childhood and adolescence

The safety and effectiveness of telmisartan in children and adolescents under 18 years of age have not been established.

Pharmacokinetics

When taken orally, it is quickly absorbed from the gastrointestinal tract (GIT). Bioavailability – 50%. The reduction in the area under the concentration-time curve (AUC) when telmisartan is administered concomitantly with food ranges from 6% (at a dose of 40 mg) to 19% (at a dose of 160 mg). 3 hours after administration, the concentration in the blood plasma levels off, regardless of the time of meal. There is a difference in plasma concentrations between men and women. The maximum plasma concentration (Cmax) and AUC in women compared to men were approximately 3 and 2 times higher, respectively (without a significant effect on efficacy).

Communication with blood plasma proteins is 99.5%, mainly with albumin and alpha-1 glycoprotein.

The average apparent volume of distribution at equilibrium concentration is 500 l. Metabolized by conjugation with glucuronic acid. Metabolites are pharmacologically inactive. The half-life (T½) is more than 20 hours. It is excreted primarily through the intestines unchanged and by the kidneys – less than 2% of the dose taken. The total plasma clearance is high (900 ml/min) compared to the “hepatic” blood flow (about 1500 ml/min).

Pharmacokinetics in selected patient groups

Elderly patients

The pharmacokinetics of telmisartan in elderly patients does not differ from the pharmacokinetics in young patients. No dose adjustment is required.

Patients with kidney failure

No dose adjustment is required in patients with renal impairment, including patients on hemodialysis.

Telmisartan is not removed by hemodialysis.

Patients with liver failure

In patients with mild to moderate liver dysfunction (classes A and B according to the Child-Pugh classification), the daily dose of the drug should not exceed 40 mg.

Use in pediatrics

The main pharmacokinetics of telmisartan in children aged 6 to 18 years after taking telmisartan at a dose of 1 mg/kg or 2 mg/kg for 4 weeks are generally comparable to the data obtained in the treatment of adult patients and confirm the nonlinearity of the pharmacokinetics of telmisartan, especially with respect to Cmax.

Storage conditions

At a temperature not exceeding 25 ºС, in the original packaging.

Keep out of the reach of children.

Shelf life

3 years.

Do not use the drug after the expiration date.

Manufacturer

KRKA dd Novo Mesto, Slovenia