Telsartan, tablets 40 mg 30 pcs

Pharmacodynamics

Telmisartan is a specific angiotensin II receptor antagonist (ARA) type AT1, effective when taken orally. It has high affinity for the AT1 subtype of angiotensin II receptors, through which angiotensin II action 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 angiotensin II receptor.

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, have 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 (kininase II), which 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 effects of angiotensin II. Initiation of antihypertensive action is observed within 3 hours after the first oral administration of telmisartan. The drug action lasts for 24 hours and remains significant up to 48 hours.

Distinct antihypertensive effect usually develops in 4 weeks after regular drug intake.
In patients with arterial hypertension telmisartan reduces systolic and diastolic blood pressure (BP) without affecting heart rate (HR).

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

Pharmacokinetics

absorption

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

Distribution

The binding to plasma proteins is 99.5% (mainly to albumin and alpha-1 glycoprotein). The average apparent volume of distribution at equilibrium concentration is 500 liters.

Metabolism

Metabolized by conjugation with glucuronic acid. Metabolites are pharmacologically inactive.

Elimation

The half-life (T1/2) is more than 20 hours. Excreted intestinally unchanged, renal excretion – less than 2% of the dose taken. 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 of telmisartan in men and women. Maximum plasma concentration (Cmax) is approximately 3 times and AUC approximately 2 times higher in women compared to men with no significant effect on efficacy. No dosage adjustment is required.

Elderly patients

Telmisartan pharmacokinetics 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.
Patients with severe renal impairment and patients on hemodialysis are recommended a lower starting dose of 20 mg per day.

Telmisartan is not excreted by hemodialysis.

Patients with impaired hepatic function

Pharmacokinetic studies in patients with hepatic impairment have shown increased absolute bioavailability of telmisartan to almost 100%. The T1/2 is unchanged 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

Hypertension (high blood pressure)

• Arterial hypertension.

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

Active ingredient

Telmisartan

Composition

1 tablet 40 mg contains:

Active substance:

Telmisartan 40.00 mg

Associates:

Meglumine 12.00 mg

Sodium hydroxide 3.35 mg

Povidone-K30 12.00 mg

How to take, the dosage

Orally, with water and regardless of meals.

Arterial hypertension

The initial recommended dose of Telsartan® is 1 tablet 40 mg once daily. In some patients, a dose of 20 mg per day (1/2 tablet of 40 mg) may be effective. In cases when therapeutic effect is not achieved, the maximum recommended dose of Telsartan® can be increased to 80 mg (1 tablet of 80 mg or 2 tablets of 40 mg) once daily. When deciding on dose increase it should be taken into consideration that maximal antihypertensive effect is usually achieved within 4-8 weeks after the treatment start.

Lower cardiovascular morbidity and mortality

Recommended dose of Telsartan® is 1 tablet of 80 mg once daily.
Additional BP adjustment may be required during initial treatment.

Renal dysfunction

There is limited experience with telmisartan in patients with severe renal dysfunction or those on hemodialysis. Such patients require a low starting dose of 20 mg.
Patients with mild to moderate renal impairment do not require dose adjustment.

Hepatic disorders

In patients with mild to moderate hepatic impairment the daily dose of Telsartan® should not exceed 40 mg.

Use in severe hepatic impairment is contraindicated (see section “Contraindications”).

Patients of advanced age

The dosing regimen does not require changes.

Interaction

Telsartan may increase the hypotensive effect of other antihypertensive agents. Other clinically significant interactions have not been identified.

The co-administration of Telmisartan with digoxin, warfarin, hydrochlorothiazide, glibenclamide, ibuprofen, paracetamol, simvastatin and amlodipine does not lead to clinically significant interaction. When concomitant use with digoxin an increase of 20% (in a single case by 39%) in mean minimal plasma concentrations of digoxin was observed, therefore plasma levels of digoxin should be monitored.

A 2.5-fold increase in AUC0-24 and Cmax of ramipril and ramiprilat has been observed with concomitant use of telmisartan and ramipril. The clinical significance of this phenomenon has not been established.

There have been reports of reversible increases in serum lithium concentrations and toxicity when lithium is coadministered with angiotensin II receptor antagonists, including telmisartan. In this case, monitoring of plasma lithium levels is recommended and patients should be under close medical supervision.

Concomitant treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid, cyclooxygenase-2 [COX-2] inhibitors and non-selective NSAIDs, is associated with the risk of acute renal failure in patients with dehydration.

Drugs acting on the renin-angiotensin system may have a synergistic effect. Patients receiving concomitant NSAIDs and telmisartan should adequately replenish water loss and monitor renal function at the start of treatment.

Some reduction in the antihypertensive effect of telmisartan has been reported when used concomitantly with NSAIDs.

The concomitant treatment of telmisartan with corticosteroid drugs decreases the antihypertensive effect

.

Special Instructions

Hepatic dysfunction

Telmisartan is contraindicated in patients with cholestasis, biliary obstruction or severe hepatic dysfunction (Child-Pugh class C), since telmisartan is mainly excreted with bile. Decreased drug excretion is expected in such patients. Telmisartan should be used with caution in patients with mild to moderate hepatic impairment (Child-Pugh class A or B).

Vasorenal arterial hypertension

When using drugs that affect the RAAS in patients with bilateral renal artery stenosis or stenosis of the only functioning kidney, the risk of severe arterial hypotension and renal failure is increased.

Kidney function impairment

When using telmisartan in patients with renal impairment, it is recommended to monitor serum potassium and creatinine concentration. No experience with use after recent renal transplantation has been described.

Hypovolemia

Patients with hypovolemia and/or hyponatremia due to intensive diuretic therapy, salt restriction, diarrhea or vomiting may develop symptomatic arterial hypotension, especially after the first dose of telmisartan. Water-electrolyte balance abnormalities should be corrected before initiating therapy.

Double RAAS blockade

Simultaneous use of ACE inhibitors, ARA II or aliskiren increases the risk of hypotension, hyperkalemia and renal function disorders (including acute renal failure), therefore the combination of these drugs is regarded as double RAAS blockade.
Concomitant administration of ARA II with drugs containing aliskiren is contraindicated in patients with diabetes and/or with moderate or severe renal insufficiency (FFR less than 60 ml/min/1.73 m2 body surface area) and is not recommended in other patients. Concomitant use of ARA II with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

If absolutely necessary, therapy with dual RAAS blockade should be performed under close medical supervision and close monitoring of renal function, electrolytes and blood pressure.
Other conditions accompanied by activation of the RAAS

The patients with vascular tone and renal function determined by the RAAS activity (patients with chronic heart failure or kidney diseases, including stenosis of two renal arteries or arterial stenosis of the only kidney) may suffer from arterial hypotension, hyperazotemia, oliguria and in rare cases – acute renal failure.

Primary hyperaldosteronism

Patients with primary hyperaldosteronism are resistant to hypotensive drugs affecting the RAAS, so telmisartan is not recommended for these patients.
Stenosis of aortic and/or mitral valves, hypertrophic obstructive cardiomyopathy (HCMP)
Telmisartan should be used with caution in patients with hemodynamically significant stenosis of aortic and/or mitral valves or HCMP.

Patients with diabetes mellitus receiving insulin or hypoglycemic agents for oral administration
When using telmisartan in such patients hypoglycemia may develop. It is recommended to monitor blood glucose concentration regularly and adjust the dose of hypoglycemic agents if necessary.

Hyperkalemia

The use of drugs affecting the RAAS may cause hyperkalemia. Before concomitant use of such drugs, the benefit/risk ratio should be evaluated.

Risk factors for hyperkalemia:

– renal insufficiency, age over 70 years, diabetes mellitus;

– Simultaneous use of drugs that affect the RAAS (ACE inhibitors, ARA II) and/or potassium-saving diuretics (spironolactone, eplerenone, triamterene, amiloride), potassium or potassium-containing salt substitutes, NSAIDs (including COX-2 selective), heparin, immunosuppressive drugs (cyclosporine or tacrolimus), and trimethoprim;

– concomitant conditions such as dehydration, acute heart failure in decompensation, metabolic acidosis, renal dysfunction, sudden progression of renal disease (infectious diseases), conditions accompanied by tissue necrosis (acute limb ischemia, rhabdomyolysis, extensive trauma).

Patients at risk should have their serum potassium concentrations closely monitored.

Ethics

ACE inhibitors and ARA II (including telmisartan) may have less pronounced antihypertensive effects in non-Hispanic patients.
This may be due to decreased renin levels in arterial hypertension in these patients compared with other races.

Other

As with any hypotensive treatment, excessive BP reduction in patients with CHD or ischemic cardiomyopathy may lead to myocardial infarction or stroke.
No special clinical studies have been conducted to evaluate the effect of the drug on the ability to drive and operate machinery. However, when driving motor transport and engaging in hazardous activities, the possibility of dizziness and somnolence should be taken into account, which requires caution.

Contraindications

• High sensitivity to the active ingredient or excipients of the drug.

• Pregnancy and lactation.

• obstructive diseases of the biliary tract.

• Severe hepatic impairment (Child-Pugh class C).

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

• Simultaneous use with angiotensin-converting enzyme inhibitors in patients with diabetic nephropathy.

• Age under 18 years of age (efficacy and safety not established).

With caution:

• Bilateral renal artery stenosis or artery stenosis of the single kidney (see “Special Indications.

• Mild to moderate hepatic and/or renal impairment (see “Special Indications”).

• Decreased circulating blood volume (CBC) due to previous diuretic therapy, restricted intake of table salt, diarrhea, or vomiting

• Hyponatremia.

• Hyperkalemia.

• Conditions after kidney transplantation (no experience of use).

• Cronic heart failure.

• Aortic and mitral valve stenosis.

• Idiopathic hypertrophic subaortic stenosis (hypertrophic obstructive cardiomyopathy).

• Primary hyperaldosteronism.
  

Side effects

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

World Health Organization (WHO) frequency classification of adverse reactions:

very common (>1/10); common (>1/100 to <1/10); infrequent (>1/1000 to <1/100); rare (>1/10,000 to < 1/1000); very rare (<1/10 000); frequency is unknown (according to available data it is impossible to establish the frequency of occurrence).

Infectious and parasitic diseases

Infrequent – upper respiratory tract infections, including pharyngitis and sinusitis, urinary tract infections (including cystitis); frequency is unknown – sepsis, including sepsis with lethal outcome.

Blood and lymphatic system disorders

Infrequent – anemia; rarely – thrombocytopenia; frequency unknown – eosinophilia.

Mental disorders

Infrequent – depression; rarely – anxiety.

Nervous system disorders

Infrequent – insomnia, syncope, vertigo; rarely – syncope.

Visual organ disorders

Rarely – visual disturbances.

Cardiac disorders

Infrequent – bradycardia; rarely – tachycardia.

Vascular disorders

Infrequent – significant decrease of 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

Infrequent – dyspnea, cough.

Gastrointestinal tract disorders

Infrequent – abdominal pain, diarrhea, dyspepsia, flatulence, vomiting; rarely – stomach upset, discomfort, dry oral mucosa, liver disorders/liver disease.

Immune system disorders

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

Dermatological and subcutaneous tissue disorders

Infrequent – hyperhidrosis, itching, rash; rarely – erythema, drug rash, toxic skin rash, eczema, frequency unknown – urticaria.

Muscular and connective tissue disorders

Infrequent – myalgia, back pain (such as sciatica), muscle spasms; infrequent – arthralgia, pain in the extremities; frequency unknown – pain in the tendon area (tendinitis-like symptoms).

Renal and urinary tract disorders

Infrequent – renal failure, including acute renal failure.

Disorders of metabolism and nutrition

Infrequent – hyperkalemia.

General disorders

Infrequent – chest pain, asthenia (weakness); rarely – flu-like condition.

Laboratory and instrumental data

Infrequent – increase of blood creatinine concentration; infrequent – increased concentration of uric acid in blood, “hepatic” enzymes, creatin phosphokinase activity in blood serum, decrease of hemoglobin, hypoglycemia (in patients with diabetes).

Overdose

The data on overdose in humans is very limited.

Symptoms: The most likely signs of overdose may be hypotension and tachycardia; the development of bradycardia is also not excluded.

Treatment: The recommended treatment is symptomatic. Telmisartan is not removed from the blood by hemodialysis.

Pregnancy use

Pregnancy

Drugs acting directly on the RAAS may cause serious damage and death to the developing fetus, so if pregnancy is planned or established, the drug should be immediately withdrawn and, if necessary, an alternative hypotensive therapy with an established safety profile for use during pregnancy should be prescribed. The use of the drug during pregnancy is contraindicated.

In preclinical studies of telmisartan no teratogenic effects were found, but fetotoxicity was established. It is known that exposure to angiotensin II receptor antagonists during the second and third trimesters of pregnancy causes fetotoxicity in humans (decreased renal function, oligohydramnion, delayed cranial ossification) and neonatal toxicity (renal failure, hypotension, hyperkalemia). Alternative therapy should be administered to patients planning pregnancy. If treatment with angiotensin II receptor antagonists occurred during the second trimester of pregnancy, it is recommended to check renal function and fetal skull by ultrasound.

Newborns whose mothers have received angiotensin II receptor antagonists should be closely monitored for hypotension.

Breastfeeding

Breastfeeding is contraindicated during telmisartan therapy.

Fertility

There have been no studies of the effect on human fertility.

Similarities

Mycardis, Telsartan, Telzap, Telmista, Telpres, Telmisartan