Tanidol, 80 mg 30 pcs.

Telmisartan is a specific angiotensin II receptor antagonist (type AT1) with high affinity for the AT1 subtype of the angiotensin II receptor, through which angiotensin II action is realized.

Telmisartan does not exhibit any activity as an AT1 receptor agonist. Telmisartan selectively binds to the AT1 receptor. Binding is prolonged. Telmisartan has no affinity for other receptors, including AT2 receptor and other less studied angiotensin receptors. The functional role of these receptors is unknown, and the effect of their possible increased stimulation by angiotensin II, whose levels are increased by telmisartan, is also unknown.

Telmisartan reduces plasma aldosterone concentration, does not reduce plasma renin activity and does not block ion channels. Telmisartan does not inhibit angiotensin-converting enzyme (kininase II), which also catalyzes bradykinin degradation. This avoids the side effects associated with the action of bradykinin.

Telmisartan at a dose of 80 mg completely blocks the hypertensive effect of angiotensin II in patients. The effective action of the drug lasts more than 24 hours and is still noticeable after 48 hours.

After the first administration of telmisartan, the onset of antihypertensive action is noted within three hours. Maximum blood pressure reduction is usually achieved 4 to 8 weeks after initiation of treatment and persists with long-term treatment. The antihypertensive effect lasts more than 24 hours after taking the drug.

In patients with arterial hypertension, telmisartan reduces both systolic and diastolic blood pressure without affecting heart rate.

In case of abrupt telmisartan withdrawal, blood pressure gradually (over several days) returns to baseline values without development of “withdrawal” syndrome.

In comparative clinical studies, the incidence of dry cough was significantly lower in patients receiving telmisartan compared to those receiving angiotensin-converting enzyme inhibitors.

The efficacy of reducing cardiovascular mortality risk with telesartan doses less than 80 mg has not been studied.

Pharmacokinetics

Intake

After oral administration, telmisartan is rapidly absorbed from the gastrointestinal tract. Bioavailability is about 50%. When telmisartan is taken simultaneously with food the area under the curve “concentration – time” (AUC) for telmisartan varies from 6% (at a dose of 40 mg) to 19% (at a dose of 160 mg). Three hours after drug intake, telmisartan plasma concentrations equalize regardless of fasting or food intake.

Linearity/non-linearity

It is not expected that a slight decrease in AUC may cause a decrease in therapeutic efficacy. There is no linear relationship between dose and plasma drug concentration. At doses greater than 40 mg, the maximum plasma concentration (Cmax) and, to a lesser extent, AUC increase disproportionately.

Distribution

Telmisartan actively binds to plasma proteins (more than 99.5%), primarily to albumin and alpha-1 acidic glycoprotein. The average value of the apparent volume of distribution in the equilibrium stage (Vdss) is approximately 500 liters.

Metabolism

Telmisartan is metabolized by conjugation of the parent substance with glucuronide. No pharmacological activity of the conjugate has been detected.

Telmisartan is characterized by biexponential breakdown pharmacokinetics with a final elimination half-life of more than 20 hours. The maximum plasma concentration (Cmax) and, to a lesser extent, the area under the concentration-time curve (AUC) increase disproportionately with dose. There is no evidence that the accumulation of telmisartan at recommended doses is clinically relevant. Plasma concentrations were higher in women compared to men, but no corresponding effect on efficacy was noted.

After oral (and intravenous) administration, telmisartan is excreted almost exclusively through the intestine, mostly unchanged. The total amount excreted by the kidneys is less than 1% of the dose. Total plasma clearance (Cltot) is high (about 1000 ml/min) compared to hepatic blood flow (about 1500 ml/min).

Pharmacokinetics in special patient groups

Gender differences

There were differences in plasma Cmax and AUC concentrations in women compared to men; they were approximately 3 and 2 times higher, respectively.

Patients in the elderly

The pharmacokinetics of telmisartan in elderly patients and patients younger than 65 years do not differ.

Patients with renal impairment

Dose modification in patients with renal impairment is not required, including patients on hemodialysis. Telmisartan actively binds to plasma proteins in patients with renal impairment and is not excreted by dialysis. The elimination half-life in patients with renal impairment is unchanged.

Patients with hepatic impairment

Pharmacokinetic studies with patients with hepatic impairment have shown increased absolute bioavailability to almost 100%. The half-life in patients with hepatic insufficiency does not change.

Indications

– Arterial hypertension;

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

Active ingredient

Composition

Active ingredient:

Telmisartan 80 mg.

The excipients:

sodium hydroxide 6.70 mg,

povidone-C25 24.00 mg,

meglumine 24.00 mg,

lactose monohydrate 434.70 mg,

/p>

crospovidone 24.00 mg,

iron oxide yellow dye 0.60 mg,

magnesium stearate 6.00 mg.

The film jacket (opadray yellow) 18.00 mg: hypromellose-5cP 10.817 mg, titanium dioxide 5.409 mg, macrogol-400 1.082 mg, talc 0.346 mg, iron oxide yellow dye 0.346 mg.

How to take, the dosage

Ingestion, regardless of food intake.

Hypertension

The initial dose is usually 40 mg once daily. If blood pressure targets are not achieved, the drug dose may be increased to the maximum dose (80 mg) once daily. Alternatively, Tanidol® can be used in combination with thiazide diuretics, such as hydrochlorothiazide, which has demonstrated an additive antihypertensive effect when used simultaneously.

When increasing the dose is necessary, it should be taken into account that the maximum antihypertensive effect usually develops 4-8 weeks after the start of treatment.

Lower cardiovascular morbidity and mortality

The recommended dose is 80 mg once daily. Regular monitoring of blood pressure and, if necessary, adjustment of the dose of blood pressure lowering drugs is recommended.

Particular patient populations

Renal impairment: Patients with mild to moderate renal impairment do not require dose adjustments. There is limited experience with use in patients with severe renal impairment or patients requiring hemodialysis.

Hepatic failure: In patients with mild to moderate hepatic failure, the daily dose of the drug should not exceed 40 mg.

Patients in the elderly

There is no need to adjust the dose for elderly patients.

Children

Tanidol® is not recommended for use in children under 18 years of age because of insufficient data on safety and effectiveness.

Interaction

Angiotensin-converting enzyme (ACE) inhibitors, potassium-saving diuretics

. When ACE inhibitors, potassium-saving diuretics (spironolactone, eplerenone, triamterene or amiloride) and other drugs that can increase serum potassium levels, as well as potassium-containing food supplements are prescribed simultaneously, especially in patients with renal insufficiency, the risk of hyperkalemia increases. Regular control of serum potassium is necessary. Concomitant use is not recommended.

Lithium preparations

When concomitant use of lithium preparations with ACE inhibitors and angiotensin II receptor antagonists, including telmisartan, a reversible increase in serum lithium concentrations has been noted. Close monitoring of serum lithium concentrations is recommended. Concomitant use requires caution.

Digoxin

Telmisartan increases digoxin concentrations by an average of 20% (39% in one case); determination of digoxin concentrations during concomitant use is necessary.

Warfarin

Telmisartan reduces (slightly) the plasma concentration of warfarin.

Risperidone

Enhances the antihypertensive effect of telmisartan.

Non-steroidal anti-inflammatory drugs (NSAIDs)

NSAIDs (e.g., acetylsalicylic acid in doses with anti-inflammatory effects, cyclooxygenase inhibitors (COX-2) and non-selective non-steroidal anti-inflammatory drugs) may decrease the antihypertensive effect of Tanidol®.

In patients with impaired renal function (e.g., patients with decreased circulating blood volume (CBV) or elderly patients with impaired renal function) the simultaneous use of Tanidol® and agents which inhibit cyclooxygenase may cause further impairment of renal function, including possible acute renal failure which is usually reversible. Caution should be exercised with concomitant administration, especially in elderly patients. Renal function should be monitored after initiation of combined therapy and periodically thereafter.

Diuretics (thiazide or “loop” diuretics)

. Prior therapy with high doses of diuretics such as furosemide (“loop” diuretic) and hydrochlorothiazide (thiazide-type diuretic) may result in decreased body fluid volume and increased risk of arterial hypotension at the start of therapy with Tanidol®.

Other hypotensive agents

The antihypertensive effect of the drug Tanidol® may be enhanced when used in combination with other hypotensive agents. On the basis of data on pharmacological properties it can be assumed that the following drugs can enhance the antihypertensive effect of all hypotensive agents, including telmisartan: baclofen, amifosten.

Ethanol, barbiturates, narcotics, or antidepressants may increase orthostatic hypotension.

Corticosteroids (systemic action)

Decrease the antihypertensive effect of telmisartan.

Special Instructions

Before and during treatment with Tanidol® it is necessary to control blood pressure, renal function, serum potassium content. Transient arterial hypotension is not a contraindication for further treatment with the drug Tanidol® after arterial pressure stabilization. In case of recurrent severe arterial hypotension the dose should be reduced or the drug should be discontinued. In case of renal insufficiency the treatment is carried out with caution under control of serum creatinine concentration.

Hepatic failure

Tanidol® should not be used in patients with cholestasis, biliary obstruction or acute hepatic failure because telmisartan is mainly excreted with bile. The hepatic clearance of telmisartan is presumed to be reduced in such patients. Tanidol® should be used with extreme caution in patients with mild to moderate hepatic impairment.

Renovascular hypertension

The treatment with drugs acting on the renin-angiotensin-aldosterone system (RAAS) increases the risk of severe arterial hypotension and renal failure in patients with bilateral renal artery stenosis and artery stenosis of the single kidney.

Renal failure and renal transplantation

When using Tanidol® in patients with impaired renal function, periodic monitoring of serum potassium and creatinine is recommended. There is no clinical experience of using the drug Tanidol® in patients who have recently undergone renal transplantation.

Decreased circulating blood volume (CBC)

In patients with decreased CBC and/or sodium content due to previous diuretic therapy, restriction of table salt intake, diarrhea or vomiting, symptomatic arterial hypotension may occur, especially after the first use of Tanidol®. Such conditions should be eliminated before taking it. Deficiency of fluid and/or sodium should be eliminated before taking the drug Tanidol®.

Double blockade of the renin-angiotensin-aldosterone system

As consequences of RAAS inhibition have been noted: The occurrence of arterial hypotension, syncope, hyperkalemia, and impaired renal function (including acute renal failure) in predisposed patients, especially when used in combination with drugs that also act on this system. Dual RAAS blockade, such as when adding an ACE (angiotensin converting enzyme) inhibitor to an angiotensin II receptor antagonist, is not recommended for patients with already controlled blood pressure and should be limited to individual cases with enhanced renal function monitoring.

Other diseases characterized by RAAS stimulation

. In patients whose vascular tone and renal function are predominantly dependent on RAAS activity (e.g., patients with chronic heart failure or renal disease, including renal artery stenosis), use of drugs acting on this system, such as telmisartan, has been associated with the occurrence of acute arterial hypotension, hyperazotemia, oliguria or rarely with acute renal failure.

Primary aldosteronism

Patients with primary aldosteronism generally do not respond to treatment with hypotensive medications whose effect is to inhibit the RAAS. Due to this reason the use of the drug Tanidol® is not recommended in these cases.

Aortic and mitral valve stenosis, hypertrophic obstructive cardiomyopathy

As with other vasodilators, special precautions are indicated for patients with aortic imitral stenosis or hypertrophic obstructive cardiomyopathy.

Hyperkalemia

The use of drugs acting on the RAAS may cause hyperkalemia.

In elderly patients, patients with renal insufficiency, patients with diabetes mellitus and also with arterial hypertension and coronary heart disease (CHD), patients receiving concomitant therapy with drugs that may cause potassium increase, and/or patients with comorbidities, hyperkalemia may be fatal.

Before considering concomitant use of drugs that act on the RAAS, the benefit-risk ratio should be evaluated.

The main risk factors to consider are:

– Diabetes mellitus, renal impairment, age (patients over 70 years of age).

– Combination with one or more drugs acting on the RAAS and/or increased serum potassium. Drugs or therapeutic classes of drugs that may cause hyperkalemia are salt substitutes containing potassium, potassium-saving diuretics, ACE inhibitors, angiotensin II receptor antagonists, nonsteroidal drugs (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, acute renal impairment (e.g., infectious diseases), cytolysis syndrome (e.g., acute limb ischemia, rhabdomyolysis, severe trauma). For patients at risk, regular monitoring of serum potassium is recommended.

Lactose

This drug contains lactose monohydrate. Patients with rare hereditary diseases, such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose absorption disorders, should not take this medication.

Racial differences

. As noted for angiotensin-converting enzyme (ACE) inhibitors, Tanidol® and other angiotensin II receptor antagonists appear to reduce blood pressure less effectively in non-Hispanic patients than in other races, possibly because of a greater predisposition to decreased renin activity in the non-Hispanic patient population, patients with diabetes and also with hypertension and CHD.

Other

As with other hypotensive agents, excessive lowering of blood pressure in patients with coronary artery disease or patients with diabetes and also with arterial hypertension and CHD may lead to myocardial infarction or impaired cerebral circulation.

Impact on the ability to drive vehicles and operate machinery

There have been no special studies of the effect of the drug on the ability to drive vehicles and operate machinery. Caution is necessary when driving vehicles and operating machinery (risk of dizziness and drowsiness).

Contraindications

With caution

. Bilateral renal artery stenosis, artery stenosis of the single kidney, renal and/or hepatic dysfunction, post kidney transplant condition (no experience of use), reduced circulating blood volume due to previous diuretic therapy, restriction of intake of table salt, diarrhea or vomiting, hyponatremia, hyperkalemia, chronic heart failure, aortic and/or mitral valve stenosis, hypertrophic obstructive cardiomyopathy, CHD.

Side effects

In general, the incidence of adverse events noted for telmisartan (41.4%) was comparable to that of placebo (43.9%). The incidence of adverse events was not dose-dependent and did not correlate with patient gender, age, or race.

Adverse adverse reactions were presented according to frequency of occurrence: very common (≥ 1/10); common (≥ 1/100 to < 1/10); infrequent (≥ 1/1000 to < 1/100); rare (≥ 1/10000 to < 1/1000); very rare (< 1/10000), unknown frequency (no estimate could be made based on available data).

In each frequency group, adverse adverse reactions are presented in decreasing order of severity.

Infections and invasions

Infrequent: upper respiratory tract infection, including pharyngitis and sinusitis, urinary tract infection, including cystitis; Unknown frequency: sepsis, including fatal.

Blood and lymphatic system disorders

Infrequent: anemia; Rarely: thrombocytopenia; Unknown frequency: eosinophilia.

Immune system disorders

Rarely: hypersensitivity;

Unknown frequency: anaphylactic reactions.

Disorders of nutrition and metabolism

Infrequent: hyperkalemia.

Mental disorders

Infrequent: depression, insomnia;

Rarely: anxiety.

Nervous system disorders

Infrequent: syncope.

Visual system disorders

Rarely: visual impairment.

Hearing and balance disorders

Infrequent: vertigo.

Cardiovascular system disorders

Infrequent: bradycardia, significant decrease in blood pressure*, orthostatic hypotension;

Rarely: tachycardia.

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

Respiratory, thoracic and mediastinal disorders

Infrequent: dyspnea.

Gastrointestinal system disorders

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

Rarely: gastric distress, discomfort, dry oral mucosa.

Hepatobiliary system disorders

Rarely: impaired liver function/liver disease.

Skin and subcutaneous tissue disorders

Infrequent: hyperhidrosis, skin itching, rash; Rare: erythema, angioedema (including fatal), 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).

Disorders of the urinary system

Infrequent: renal failure, including acute renal failure.

Systemic disorders

Infrequent: chest pain, asthenia (weakness); Rare: flu-like condition.

Laboratory indices

Infrequent: increased concentration of creatinine in blood; Rare: increased concentration of uric acid in blood, “hepatic” enzymes, serum creatinphosphokinase activity; decrease of hemoglobin; hypoglycemia (in patients with diabetes).

Overdose

Information regarding overdose is limited.

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

Treatment: treatment should be symptomatic and supportive. Suggested measures include: inducing vomiting and/or gastric lavage, intake of activated charcoal, replenishment of liquid and salt deficiencies. Serum electrolytes and creatinine should be monitored continuously. Hemodialysis is not effective.

Similarities