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;

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

Pharmacological effect

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

Telmisartan does not exhibit any activity as an AT1 receptor agonist. Telmisartan selectively binds to the AT1 receptor. The binding is long lasting. Telmisartan does not show affinity for other receptors, including the 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, the level of which increases under the influence of telmisartan, is also unknown.

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

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

After the first dose of telmisartan, the onset of antihypertensive action is observed within three hours. The maximum reduction in blood pressure is usually achieved 4 to 8 weeks after the start 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 withdrawal of telmisartan, blood pressure gradually (within several days) returns to initial values ​​without the 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 effectiveness of reducing the risk of cardiovascular mortality with doses of telmisartan less than 80 mg has not been studied.

Pharmacokinetics

Suction

After oral administration, telmisartan is rapidly absorbed from the gastrointestinal tract. Bioavailability is about 50%. When telmisartan is taken simultaneously with food, the reduction in the area under the concentration-time curve (AUC) for telmisartan varies from 6% (at a dose of 40 mg) to 19% (at a dose of 160 mg). 3 hours after taking the drug, the concentrations of telmisartan in the blood plasma level out, regardless of taking the drug on an empty stomach or with food.

Linearity/nonlinearity

A slight decrease in AUC is not expected to cause a decrease in therapeutic efficacy. There is no linear relationship between the dose and the concentration of the drug in the blood plasma. 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%), mainly to albumin and alpha-1 acid glycoprotein. The average apparent volume of distribution at equilibrium (Vdss) is approximately 500 L.

Metabolism

Telmisartan is metabolized through conjugation of the parent substance with a glucuronide. No pharmacological activity of the conjugate was detected.

Removal

Telmisartan exhibits biexponential decay pharmacokinetics with a terminal 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 when taken at recommended doses is of clinical significance. Plasma concentrations were higher in women compared to men, but no corresponding effect on efficacy was observed.

After administration of the drug orally (and intravenously), telmisartan is excreted almost exclusively through the intestines, mainly 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 groups of patients

Gender differences

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

Elderly patients

The pharmacokinetics of telmisartan in elderly patients and patients under 65 years of age does not differ.

Patients with renal failure

No dose adjustment is required in patients with renal impairment, including patients on hemodialysis. Telmisartan actively binds to plasma proteins in patients with renal failure and is not excreted during dialysis. The half-life does not change in patients with renal failure.

Patients with liver failure

Pharmacokinetic studies in patients with liver failure revealed an increase in absolute bioavailability to almost 100%. The half-life does not change in patients with liver failure.

Special instructions

Before starting and during treatment with Tanidol®, monitoring of blood pressure, kidney function, and potassium levels in the blood serum is necessary. Transient arterial hypotension is not a contraindication for further treatment with Tanidol® after stabilization of blood pressure. If severe arterial hypotension reoccurs, the dose should be reduced or the drug discontinued. In the presence of renal failure, treatment is carried out with caution under the control of serum creatinine concentration.

Liver failure

Tanidol® should not be used in patients with cholestasis, biliary obstruction or acute liver failure, since telmisartan is mainly excreted in the bile. It is assumed that in such patients the hepatic clearance of telmisartan is reduced. Tanidol® should be used with extreme caution in patients with mild or moderate hepatic impairment.

Renovascular hypertension

When treated with drugs acting on the renin-angiotensin-aldosterone system (RAAS), the risk of severe arterial hypotension and renal failure increases in patients with bilateral renal artery stenosis and stenosis of the artery of a solitary kidney.

Kidney failure and kidney transplantation

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

Decrease in circulating blood volume (CBV)

In patients with a decrease in blood volume and/or sodium content due to previous diuretic therapy, restriction of salt intake, diarrhea or vomiting, symptomatic arterial hypotension may occur, especially after the first dose of Tanidol®. Such conditions must be eliminated before taking it. Fluid and/or sodium deficiency must be corrected before starting to take Tanidol®.

Dual blockade of the renin-angiotensin-aldosterone system

The following consequences of RAAS inhibition have been noted: the occurrence of arterial hypotension, fainting, 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 blockade of the RAAS, for example by adding an ACE inhibitor (angiotensin-converting enzyme) to an angiotensin II receptor antagonist, is not recommended for patients with already controlled blood pressure and should be limited to selected cases with increased monitoring of renal function.

Other diseases characterized by stimulation of the RAAS

In patients whose vascular tone and renal function depend primarily on the activity of the RAAS (for example, patients with chronic heart failure or kidney disease, including renal artery stenosis), the 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 antihypertensive drugs that act by inhibiting the RAAS. In this regard, the use of Tanidol® in these cases is not recommended.

Aortic and mitral valve stenosis, hypertrophic obstructive cardiomyopathy

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

Hyperkalemia

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

For elderly patients, patients with renal failure, patients with diabetes mellitus and also with arterial hypertension and coronary artery disease (CHD), patients receiving concomitant therapy with drugs that can cause an increase in potassium levels, and/or patients with concomitant disease, hyperkalemia can be fatal.

Before considering the possibility of concomitant use of drugs acting on the RAAS, it is necessary to assess the benefit-risk ratio.

The main risk factors to consider are:

– Diabetes mellitus, renal failure, age (patients over 70 years old).

– Combination with one or more drugs acting on the RAAS and/or increasing serum potassium levels. Drugs or therapeutic classes of drugs that may cause hyperkalemia include potassium-containing salt substitutes, potassium-sparing 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 deterioration of kidney condition (for example, infectious diseases), cytolysis syndrome (for example, acute limb ischemia, rhabdomyolysis, severe trauma). For patients at risk, regular monitoring of serum potassium levels is recommended.

Lactose

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

Racial differences

As noted for angiotensin-converting enzyme (ACE) inhibitors, Tanidol® and other angiotensin II receptor antagonists 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 the black patient population, patients with diabetes mellitus and also with hypertension and coronary artery disease.

Other

As with the use of other antihypertensive drugs, an excessive decrease in blood pressure in patients suffering from ischemic cardiopathy or patients with diabetes mellitus and also with arterial hypertension and coronary artery disease can lead to the development of myocardial infarction or cerebrovascular accident.

Impact on the ability to drive vehicles and work with equipment

No special studies have been conducted on the effect of the drug on the ability to drive vehicles or operate machinery. Care must be taken when driving vehicles, as well as when working with equipment (risk of dizziness and drowsiness).

Active ingredient

Telmisartan

Composition

Active ingredient:

telmisartan 80 mg.

Excipients:

sodium hydroxide 6.70 mg,

povidone-K25 24.00 mg,

meglumine 24.00 mg,

lactose monohydrate 434.70 mg,

crospovidone 24.00 mg,

iron dye yellow oxide 0.60 mg,

magnesium stearate 6.00 mg.

Film coating (opadry yellow) 18.00 mg: hypromellose-5cP 10.817 mg, titanium dioxide 5.409 mg, macrogol-400 1.082 mg, talc 0.346 mg, iron dye yellow oxide 0.346 mg.

Contraindications

Hypersensitivity to the active substance or other components of the drug;
Pregnancy and lactation;
Obstructive diseases of the biliary tract;
Children’s age (up to 18 years);
Lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
Severe liver dysfunction (class C on the Child-Pugh scale (10-15 points));
Primary aldosteronism.

With caution

Bilateral renal artery stenosis, stenosis of the artery of a single kidney, impaired renal and/or liver function, condition after kidney transplantation (no experience with use), decreased circulating blood volume due to previous diuretic therapy, limited salt intake, diarrhea or vomiting, hyponatremia, hyperkalemia, chronic heart failure, aortic and/or mitral valve stenosis, hypertrophic obstructive cardiomyopathy, ischemic heart disease.

Side Effects

Overall, the incidence of adverse events observed for telmisartan (41.4%) was comparable to that for placebo (43.9%). The incidence of adverse events was not dose dependent and did not correlate with gender, age, or race of patients.

Adverse adverse reactions are presented according to frequency of occurrence: very common (≥ 1/10); often (from ≥ 1/100 to < 1/10); uncommon (from ≥ 1/1000 to < 1/100); rare (from ≥ 1/10000 to < 1/1000); very rare (< 1/10000), unknown frequency (cannot be estimated from available data).

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

Infections and infestations

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

Blood and lymphatic system disorders

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

Immune system disorders

Rarely: hypersensitivity;

Unknown frequency: anaphylactic reactions.

Nutritional and metabolic disorders

Uncommon: hyperkalemia.

Mental disorders

Uncommon: depression, insomnia;

Rarely: anxiety.

Nervous system disorders

Uncommon: syncope.

Visual disorders

Rarely: visual impairment.

Hearing and balance disorders

Uncommon: vertigo.

Cardiovascular disorders

Uncommon: bradycardia, marked decrease in blood pressure*, orthostatic hypotension;

Rarely: tachycardia.

*Commonly 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

Uncommon: shortness of breath.

Digestive system disorders

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

Rarely: stomach upset, discomfort, dry oral mucosa.

Hepatobiliary system disorders

Rare: liver dysfunction/liver disease.

Skin and subcutaneous tissue disorders

Uncommon: hyperhidrosis, itching, rash; Rarely: erythema, angioedema (including fatal), drug rash, toxic skin rash, eczema; Unknown frequency: urticaria.

Musculoskeletal and connective tissue disorders

Uncommon: myalgia, back pain (eg, sciatica), muscle spasms; Rarely: arthralgia, pain in the extremities; Unknown frequency: pain in the tendon area (tendinitis-like symptoms).

Urinary system disorders

Uncommon: renal failure, including acute renal failure.

Systemic disorders

Uncommon: chest pain, asthenia (weakness); Rarely: flu-like condition.

Laboratory indicators

Uncommon: increased creatinine concentration in the blood; Rarely: increased concentration of uric acid in the blood, liver enzymes, creatine phosphokinase activity in the blood serum; decrease in hemoglobin; hypoglycemia (in patients with diabetes).

Interaction

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

With the simultaneous administration of ACE inhibitors, potassium-sparing diuretics (spironolactone, eplerenone, triamterene or amiloride) and other drugs that can increase the level of potassium in the blood serum, as well as potassium-containing nutritional supplements, especially in patients with renal failure, the risk of developing hyperkalemia increases. Regular monitoring of serum potassium levels is necessary. Combined use is not recommended.

Lithium preparations

When taking lithium preparations simultaneously with ACE inhibitors and angiotensin II receptor antagonists, including telmisartan, a reversible increase in serum lithium concentrations was observed. It is recommended to carefully monitor serum lithium concentrations. Concomitant use requires caution.

Digoxin

Telmisartan increases digoxin concentrations by an average of 20% (in one case by 39%); it is necessary to determine the concentration of digoxin during simultaneous use.

Warfarin

While taking telmisartan, the concentration of warfarin in the blood plasma decreases (slightly).

Risperidone

Enhances the antihypertensive effect of telmisartan.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs (for example, acetylsalicylic acid in doses that have an anti-inflammatory effect, cyclooxygenase (COX-2) inhibitors and non-selective non-steroidal anti-inflammatory drugs) may reduce the antihypertensive effect of Tanidol®.

In patients with impaired renal function (for example, patients with reduced circulating blood volume (BCV) or elderly patients with impaired renal function), concomitant use of Tanidol® and drugs that inhibit cyclooxygenase may cause an even greater deterioration of renal function, including possible acute renal failure, which is usually reversible. Caution should be exercised during concomitant use, especially in elderly patients. Renal function should be monitored after initiation of combination therapy and periodically thereafter.

Diuretics (thiazide or loop diuretics)

Pre-therapy with high doses of diuretics, such as furosemide (loop diuretic) and hydrochlorothiazide (thiazide-type diuretic), can lead to a decrease in body fluid volume and an increased risk of arterial hypotension at the beginning of therapy with Tanidol®.

Other antihypertensive drugs

The antihypertensive effect of Tanidol® can be enhanced when used together with other antihypertensive drugs. Based on data on pharmacological properties, it can be assumed that the following drugs can enhance the antihypertensive effect of all antihypertensive drugs, including telmisartan: baclofen, amifostene.

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

Corticosteroids (systemic)

Reduced antihypertensive effect of telmisartan.

Overdose

Information regarding overdose is limited.

Symptoms: the most significant are a pronounced decrease in blood pressure and tachycardia; Bradycardia, dizziness, increased serum creatinine concentrations, and acute renal failure may also occur.

Treatment: Treatment should be symptomatic and supportive. Suggested measures include: inducing vomiting and/or gastric lavage, taking activated charcoal, replenishing the lack of fluids and salts. The content of electrolytes and creatinine in the blood serum should be constantly monitored. Hemodialysis is not effective.

Storage conditions

At a temperature not exceeding 30 °C. Keep out of the reach of children!

Shelf life

3 years.

Do not use after the expiration date stated on the package.

Manufacturer

Glenmark Pharmaceuticals Ltd/Gedeon Richter, India