Telprez, tablets 20 mg 28 pcs

Pharmacotherapeutic group:

An angiotensin II receptor antagonist

ATC:

C.09.C.A.07 Telmisartan

Pharmacodynamics:

Telmisartan is a specific angiotensin II receptor antagonist (type AT1) effective when taken orally. It has high affinity for the AT1 subtype of angiotensin II receptors, through which the action of angiotensin II is realized. It displaces angiotensin II from binding to the receptor, having no agonist effect against this receptor. Telmisartan binds only to the AT1 subtype of the angiotensin II receptor. The binding is long-lasting. It has no affinity for other receptors, including AT2 receptor and other less studied angiotensin receptors. The functional significance of these receptors and the effect of their possible overstimulation by angiotensin II, the concentration of which increases with telmisartan administration, has not been studied. It reduces the blood concentration of aldosterone, does not inhibit plasma renin and does not block ion channels. Telmisartan does not inhibit angiotensin-converting enzyme (kinininase II) (an enzyme that also degrades bradykinin). Therefore, an increase in bradykinin-induced side effects is not expected.

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

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

In case of abrupt telmisartan withdrawal, BP gradually returns to baseline levels without development of “withdrawal” syndrome.

Pharmacokinetics:

Absorption

In the oral administration, it is rapidly absorbed from the gastrointestinal tract. The bioavailability is about 50%. When taken concomitantly with food, the AUC (area under the curve “concentration-time”) decrease ranges from 6% (at a dose of 40 mg) to 19% (at a dose of 160 mg). Three hours after ingestion, plasma concentrations level off regardless of food intake.

Distribution

The binding to plasma proteins is 99.5%, mainly to albumin and alpha-1 glycoprotein. Average apparent volume of distribution at equilibrium concentration is 500 l.

Metabolism

Metabolized by conjugation with glucuronic acid. The metabolites are pharmacologically inactive.

Elimination

The elimination half-life (T1/2) is more than 20 hours. It is excreted intestinally unchanged, renal excretion – less than 2% of the administered dose. Total plasma clearance is high (900 ml/min) compared to “hepatic blood flow” (about 1500 ml/min).

Pharmacokinetics in special patient groups

Gender differences

There is a difference in plasma concentrations in men and women. Cmax (maximum concentration) and AUC were approximately 3 and 2 times higher in women compared to men, respectively, with no significant effect on efficacy. No dose adjustment is required.

Elderly patients

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

Patients with impaired renal function

In patients with mild to moderate impaired renal function, no dose adjustment of telmisartan is required.

In patients with severe renal impairment and patients on hemodialysis, a lower starting dose of 20 mg daily is recommended.

Telmisartan is not excreted by hemodialysis.

Patients with impaired hepatic function

Pharmacokinetics studies in patients with hepatic impairment have shown an increase in the absolute bioavailability of telmisartan to almost 100%.

The T1/2 is not altered in hepatic insufficiency. In patients with mild to moderate hepatic impairment (Child-Pugh class A and B) the daily dose of the drug should not exceed 40 mg.

Indications

– Arterial hypertension;

– Reduction in cardiovascular morbidity and mortality in patients aged 55 years and older with a high risk of cardiovascular disease.

Active ingredient

Composition

Each 20 mg tablet contains:

the active ingredient:

telmisartan – 20.00 mg;

excipients:

sodium hydroxide – 1.70 mg,

povidone-K25 – 5.40 mg,

meglumine – 6.00 mg,

mannitol – 81.90 mg,

magnesium stearate – 2.00 mg,

crospovidone – 3.00 mg.

How to take, the dosage

Orally, regardless of meals.

Hypertension

The initial recommended dose of Telprez is 1 tablet (40 mg) once daily. In cases when therapeutic effect is not achieved the maximum recommended dose of Telprez may be increased to 80 mg once daily. When deciding on increasing 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.

Lower cardiovascular morbidity and mortality

The recommended dose is 1 tablet of Telprez 80 mg once daily.

In the initial period of treatment, monitoring of blood pressure (BP) is recommended; correction of antihypertensive therapy may be necessary.

Renal dysfunction

In patients with severe renal dysfunction and patients on hemodialysis, experience with use is limited. In these patients, the recommended starting dose is 20 mg daily. No dose adjustment is required in patients with mild to moderate renal dysfunction.

Hepatic impairment

In patients with mild to moderate hepatic impairment (Child-Pugh grades A and B, respectively) the daily dose of Telpras should not exceed 40 mg.

Elderly patients

Dose adjustment is not required in elderly patients.

Interaction

Telmisartan may increase the antihypertensive effect of other antihypertensive agents. Other interactions of clinical relevance have not been identified. Combined use with digoxin, warfarin, hydrochlorothiazide, glibenclamide, ibuprofen, paracetamol, simvastatin and amlodipine does not lead to clinically significant interactions.

Double blockade of the renin-angiotensin-aldosterone system (RAAS).

The concomitant use of telmisartan with aliskiren is contraindicated in patients with diabetes mellitus or renal insufficiency (FFR less than 60 ml/min/1.73 m2 body surface area) and is not recommended in other patients. Simultaneous use of telmisartan and AG1F inhibitors is contraindicated in patients with diabetic nephropathy.

The data from clinical studies have shown that dual RAAS blockade due to combined use of ACE inhibitors, ARA II or aliskiren is associated with an increased incidence of adverse events such as arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure) compared to use of a single drug acting on RAAS alone.

. The risk of hyperkalemia may increase when co-administered with other drugs that can cause hyperkalemia (potassium-containing supplements and salt substitutes containing potassium and potassium-saving diuretics (spironolactone eplerenone, triamterene or amiloride), nonsteroidal anti-inflammatory drugs (NSAIDs, including selective cyclooxygenase-2 (COX) inhibitors), heparin, immunosuppressants (cyclosporine, tacrolimus, trimethoprim). If it is necessary against the background of documented hypokalemia, co-administration of drugs should be performed with caution and plasma potassium content should be regularly monitored.

Digoxin

The co-administration of telmisartan with digoxin has resulted in a 49% increase in mean plasma Cmax of digoxin and a 20% increase in minimum concentration. Plasma digoxin concentrations should be carefully monitored at initiation of treatment, dose selection, and discontinuation of telmisartan treatment to maintain them within the therapeutic range.

Kalium-saving diuretics or potassium-containing supplements

Angiotensin II receptor antagonists, such as telmisartan, reduce diuretic-induced potassium loss. Potassium-saving diuretics such as spironolactone, eplerenone, triamterene, or amiloride, potassium-containing supplements, or salt substitutes may result in a significant increase in plasma potassium. If concomitant use is indicated because there is documented hypokalemia, these should be used with caution and with regular monitoring of plasma potassium.

Lithium preparations

The co-administration of lithium preparations with ACE inhibitors and ARAII inhibitors, including telmisartan, has resulted in reversible increases in plasma lithium concentration and its toxic effects. Careful monitoring of plasma lithium concentrations is recommended if this combination of drugs is necessary.

Non-steroidal anti-inflammatory drugs (NSAIDs)

NSAIDs (including acetylsalicylic acid in doses used for anti-inflammatory treatment, COX-2 inhibitors and non-selective NSAIDs) may weaken the antihypertensive effect of APAII. In some patients with impaired renal function (e.g., patients with dehydration, elderly patients with impaired renal function), coadministration of ARII and drugs that inhibit cyclooxygenase-2 may lead to further deterioration of renal function, including development of acute renal failure, which is usually reversible. Therefore, coadministration of drugs should be used with caution, especially in elderly patients. Adequate fluid intake should be ensured, and renal function parameters should be monitored at the beginning of coadministration and periodically thereafter.

Diuretics (thiazide or loop diuretics)

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

Other antihypertensive agents

The effects of telmisartan may be enhanced when other antihypertensive drugs are used together. Based on the pharmacological properties of baclofen and amifostine, it can be assumed that they will enhance the therapeutic effect of all antihypertensive agents, including telmisartan. In addition, orthostatic hypotension may be increased with alcohol, barbiturates, narcotics or antidepressants.

Corticosteroids (for systemic use)

Corticosteroids impair the effects of telmisartan.

Special Instructions

Hepatic disorders

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

Renovascular hypertension

The treatment with drugs acting on the RAAS increases the risk of severe arterial hypotension and renal failure in patients with bilateral arterial stenosis or arterial stenosis of the only functioning kidney.

Kidney dysfunction and renal transplantation

In patients with impaired renal function, periodic monitoring of plasma potassium and creatinine is recommended during use of Telprez. There is no experience in clinical use of Telprez in patients with recent kidney transplantation.

Decrease in circulating blood volume

Symptomatic arterial hypotension, especially after the first administration of Telprez, may occur in patients with decreased RBC and/or plasma sodium content due to previous treatment with diuretics, restriction of table salt intake, diarrhea or vomiting. Such conditions (fluid and/or sodium deficiency) should be eliminated prior to initiation of Telprez therapy.

Double blockade of the renin-angiotensin-aldosterone system

The concomitant use of telmisartan with aliskiren is contraindicated in patients with diabetes mellitus or renal impairment (glomerular filtration rate less than 60 ml/min/1.73 m2) (see section “Contraindications”).

The concomitant use of telmisartan and ACE inhibitors is contraindicated in patients with diabetic nephropathy (see section “Contraindications”).

As a result of RAAS inhibition, arterial hypotension, syncope, hyperkalemia and renal dysfunction (including acute renal failure) have been reported in predisposed patients, especially when several drugs that also act on this system are used together. Therefore, dual RAAS blockade (e.g., against the background of taking telmisartan with other RAAS antagonists) is not recommended.

. In cases when vascular tone and renal function depend mainly on RAAS activity (e.g., in patients with chronic heart failure or renal diseases, including renal artery stenosis or arterial stenosis of the sole kidney) the administration of agents acting on this system may be accompanied with development of acute arterial hypotension, hyperazotemia, oliguria and, in rare cases, acute renal failure.

Primary aldosteronism

In patients with primary aldosteronism, treatment with antihypertensive medications that work by inhibiting the RAAS is generally ineffective.

Aortic and mitral valve stenosis, hypertrophic obstructive cardiomyopathy

Cautious use of Telpras (as well as other vasodilators) should be observed in patients with aortic or mitral stenosis and hypertrophic obstructive cardiomyopathy.

Hyperkalemia

The administration of drugs acting on the RAAS may cause hyperkalemia. In elderly patients, patients with renal insufficiency or diabetes mellitus, patients also taking medications that increase plasma potassium, and/or patients with comorbidities, hyperkalemia can lead to death.

The risk-benefit ratio should be evaluated when deciding on concomitant use of drugs acting on the RAAS.

The main risk factors for hyperkalemia that should be considered are:

Diabetes mellitus, renal insufficiency, age (patients older than 70 years);

Combination with one or more drugs acting on the RAAS and/or potassium-containing dietary supplements. Drugs or therapeutic classes of drugs that may cause hyperkalemia include potassium-containing salt substitutes, potassium-saving diuretics, ACE inhibitors, angiotensin II receptor antagonists, nonsteroidal anti-inflammatory drugs (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 (e.g., acute limb ischemia, rhabdomyolysis, extensive trauma).

Patients at risk should have their plasma potassium carefully monitored (see section “Interaction with other medicinal products”).

Ethnic differences

The ACE inhibitors, telmisartan, and other ARAIIs appear to be less effective in lowering blood pressure in non-Hispanic patients than in other races, possibly due to a greater predisposition to lower renin activity in these patient populations.

Other

As with other antihypertensives, excessive BP lowering in patients with ischemic cardiomyopathy or coronary heart disease can lead to myocardial infarction or stroke.

The effect on the ability to drive trans. cf. and mech:

There have been no specific clinical studies of the effect of the drug on driving and operating machinery. Caution should be exercised when driving and operating machinery requiring increased concentration, as dizziness and somnolence may rarely occur while taking telmisartan.

Contraindications

– Hypersensitivity to the active ingredient or excipients of the drug;

– Pregnancy;

– Breast-feeding period;

– Obstructive biliary tract disease;

– Severe hepatic impairment (Child-Pugh class C);

The concomitant administration of – Concomitant use of Telprez with aliskiren in patients with diabetes and/or impaired renal function (glomerular filtration rate less than 60 ml/min/1.73 m2);

– Concomitant use of ACE inhibitors in patients with diabetic nephropathy;

– Age

Side effects

In general, the incidence of adverse reactions noted for telmisartan is comparable to that of placebo. The observed incidence of adverse effects did not correlate with the gender, age, or race of patients.

Infectious and parasitic diseases:

infrequent: upper respiratory tract infections, including pharyngitis and sinusitis, urinary tract infections (including cystitis);

unknown frequency: sepsis, including fatal sepsis.

Disorders of the blood and lymphatic system:

infrequent: anemia;

rare: thrombocytopenia;

unknown frequency: eosinophilia.

Psychiatric disorders:

infrequent: depression; rare: anxiety.

Nervous system disorders:

infrequent: insomnia, syncope, vertigo; rare: syncope.

Visual organ disorders:

rarely: visual disturbances.

Chronic disorders:

infrequent: bradycardia; rarely: tachycardia.

Vascular disorders:

infrequent: marked decrease in BP*, orthostatic hypotension;

* often observed in patients with controlled BP who were treated with telmisartan to reduce the risk of cardiovascular mortality in addition to standard treatment.

Disorders of the respiratory system, thoracic and mediastinal organs:

infrequently: dyspnea, cough.

Gastrointestinal disorders:

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

rarely: upset stomach, discomfort, dry oral mucosa, liver dysfunction/liver disease.

Disorders of the immune system:

Rarely: hypersensitivity, angioedema (including fatal); unknown frequency: anaphylactic reactions.

Skin and subcutaneous tissue disorders

infrequent: hyperhidrosis, skin itching, rash;

rare: erythema, drug rash, toxic skin rash, eczema, unknown frequency: urticaria.

Musculoskeletal and connective tissue disorders: infrequent: myalgia, back pain (e.g., sciatica), muscle spasms;

rarely: arthralgia, pain in the extremities;

unknown frequency: tendon pain (tendinitis-like symptoms).

Renal and urinary tract disorders:

infrequent: renal failure, including acute renal failure.

Disorders of nutrition and metabolism:

infrequent: hyperkalemia.

General disorders:

infrequent: chest pain, asthenia (weakness);

rare: flu-like condition.

Impact on the results of laboratory values and instrumental studies:

infrequent: increased blood creatinine concentration;

rare: increased blood uric acid concentration, “hepatic” enzymes, serum creatine phosphokinase activity, decreased hemoglobin, hypoglycemia (in patients with diabetes).

Overdose

Information regarding overdose is limited.

Symptoms: the most significant are marked BP decrease and tachycardia; bradycardia, dizziness, increased serum creatinine concentration and acute renal failure may also be observed.

Treatment: symptomatic and supportive. Suggested measures include: inducing vomiting and/or gastric lavage, taking activated charcoal, replenishing fluid and salt deficiencies. Continuous monitoring of serum electrolytes and creatinine. Hemodialysis is not effective.

Similarities