INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT TELNOR (TELNOR)

Composition:

Active substance: telmisartan;

One tablet contains telmisartan 20 mg or 40 mg or 80 mg;

Excipients: meglumine, mannitol, sodium hydroxide, magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties:

20 mg tablets: round, flat with beveled edges, white to almost white tablets, with the inscription "H" on one side and "162" on the reverse side;

40 mg tablets: oval, biconvex tablets, white to almost white, with the inscription "H" on one side and "163" on the reverse side;

80 mg tablets: oval, biconvex tablets, white to almost white, with the inscription "H" on one side and "164" on the reverse side.

Pharmacotherapeutic group. Simple preparations of angiotensin II antagonists.

ATC code C09CA07.

Pharmacological Properties.

Pharmacodynamics.

Mechanism of Action.

Telmisartan is a specific and potent oral angiotensin II receptor (type AT1) antagonist. Telmisartan highly selectively displaces angiotensin II from its binding sites on the AT1 receptor subtype responsible for the biological actions of ang游戏副本

Clinical characteristics.

Indications.

Hypertension.

Treatment of essential hypertension in adults.

Prevention of cardiovascular diseases.

Reduction of cardiovascular morbidity in patients with:

Manifest atherothrombotic cardiovascular disease (history of ischemic heart disease, stroke, or peripheral arterial disease);
Type 2 diabetes mellitus with documented target organ damage.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients of the drug;
Pregnancy or women planning to become pregnant (see sections "Special precautions for use", "Use during pregnancy or breastfeeding");
Biliary obstruction;
Severe hepatic impairment;
Pediatric population (under 18 years of age).

Concomitant use of telmisartan and aliskiren-containing medicinal products is contraindicated in patients with diabetes mellitus or renal impairment (GFR < 60 mL/min/1.73 m²) (see sections "Interaction with other medicinal products and other forms of interaction" and "Pharmacological properties").

Interaction with other medicinal products and other forms of interaction.

Digoxin

When telmisartan and digoxin are used concomitantly, mean increases in digoxin peak plasma concentrations (by 49%) and trough concentrations (by 20%) have been observed. Monitoring of digoxin levels should be performed at the beginning of treatment, during dose adjustments, and upon discontinuation of telmisartan to maintain levels within the therapeutic range.

As with other agents that inhibit the renin-angiotensin-aldosterone system (RAAS), telmisartan may cause hyperkalemia (see section "Special precautions for use"). The risk may be increased when used concomitantly with other agents that may also cause hyperkalemia (potassium-containing salt substitutes, potassium-sparing diuretics, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, nonsteroidal anti-inflammatory drugs (NSAIDs, including selective COX-2 inhibitors), heparin, immunosuppressants (cyclosporine or tacrolimus), and trimethoprim).

Cases of hyperkalemia depend on associated risk factors. The risk increases with the above-mentioned therapeutic combinations. The risk is particularly high when combined with potassium-sparing diuretics and with potassium-containing salt substitutes. Combination with ACE inhibitors or NSAIDs is less risky provided that appropriate precautions are strictly observed.

Concomitant use is not recommended.

Potassium-sparing diuretics or potassium supplements. Angiotensin II receptor antagonists such as telmisartan reduce potassium loss induced by diuretics. Potassium-sparing diuretics (e.g., spironolactone, eplerenone, triamterene, or amiloride), potassium-containing dietary supplements, or potassium-containing salt substitutes may lead to a significant increase in serum potassium concentration. If concomitant use is indicated due to documented hypokalemia, they should be used with caution and serum potassium levels should be monitored frequently.

Lithium. Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant use of lithium with ACE inhibitors and angiotensin II receptor antagonists, including telmisartan. These effects are generally reversible. If concomitant use is necessary, careful monitoring of serum lithium levels is recommended.

Concomitant use requires caution.

Nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs (i.e., acetylsalicylic acid at anti-inflammatory doses, COX-2 inhibitors, and non-selective NSAIDs) may reduce the antihypertensive effect of angiotensin II receptor antagonists.

In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with renal impairment), concomitant use of angiotensin II receptor antagonists and agents that inhibit cyclooxygenase may lead to further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, such combinations should be used with caution, especially in elderly patients. Patients should receive adequate fluid intake, and consideration should be given to monitoring renal function after initiation and periodically after discontinuation of concomitant therapy.

In one study, concomitant administration of telmisartan and ramipril resulted in a 2.5-fold increase in AUC₀–₂₄ and Cₘₐₓ for ramipril and ramiprilat. The clinical significance of this phenomenon is unknown.

Diuretics (thiazide or loop diuretics). Prior treatment with high doses of diuretics such as furosemide (a loop diuretic) or hydrochlorothiazide (a thiazide diuretic) may lead to dehydration and an increased risk of developing arterial hypotension at the start of telmisartan therapy.

Should be considered during concomitant use.

Other antihypertensive agents. The ability of telmisartan to lower blood pressure may be enhanced by concomitant use of other antihypertensive agents.

Clinical data have shown that dual blockade of the renin-angiotensin-aldosterone system (RAAS) by combining ACE inhibitors, angiotensin II receptor blockers, or aliskiren is associated with a higher incidence of adverse effects such as arterial hypotension, hyperkalemia, and decreased renal function (including acute renal failure) compared to use of a single RAAS-acting agent (see sections "Special precautions for use", "Contraindications", and "Pharmacodynamics").

Due to the pharmacological properties of baclofen and amifostine, it can be expected that these medicinal products may enhance the hypotensive effect of all antihypertensive agents, including telmisartan. Additionally, orthostatic hypotension may be exacerbated by alcohol consumption, barbiturates, narcotics, and antidepressants.

Corticosteroids (systemic use). Reduction of antihypertensive effect.

Special precautions for use.

Pregnancy. Angiotensin II receptor antagonists must not be initiated during pregnancy. If continuation of angiotensin II receptor antagonists is not considered essential in a woman planning pregnancy, she should be switched to an alternative antihypertensive therapy with an established safety profile during pregnancy. Angiotensin II receptor antagonists must be discontinued immediately upon confirmation of pregnancy, and alternative treatment should be initiated if necessary (see sections "Contraindications" and "Use during pregnancy or breastfeeding").

Hepatic impairment. Telmisartan is contraindicated in patients with cholestasis, biliary obstruction, or severe hepatic impairment (see section "Contraindications"), as telmisartan is primarily excreted via bile. Hepatic clearance of telmisartan is reduced in patients with these conditions.

Telmsartan should be used with caution in patients with mild to moderate hepatic impairment.

Renovascular hypertension. There is an increased risk of severe hypotension and renal failure in patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney when treated with drugs affecting the renin-angiotensin-aldosterone system (RAAS).

Renal impairment and kidney transplantation. Periodic monitoring of serum potassium and creatinine levels is recommended in patients with impaired renal function receiving telmisartan. There is no experience with the use of telmisartan in patients who have recently undergone kidney transplantation.

Reduced intravascular fluid volume. Symptomatic hypotension, particularly after the first dose of telmisartan, may occur in patients with reduced intravascular volume and/or reduced sodium levels due to intensive diuretic therapy, a low-salt diet, or diarrhoea and vomiting. These conditions should be corrected before administering telmisartan. Sodium levels and/or intravascular fluid volume should be normalized prior to initiating telmisartan therapy.

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

Evidence indicates that concomitant use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, or aliskiren increases the risk of hypotension, hyperkalaemia, and reduced renal function (including acute renal failure).

Therefore, dual blockade by combining ACE inhibitors, angiotensin II receptor blockers, or aliskiren is not recommended (see sections "Interaction with other medicinal products and other forms of interaction" and "Pharmacodynamics").

If dual blockade is considered absolutely necessary, it should be performed only under specialist supervision and with continuous, careful monitoring of renal function, electrolytes, and blood pressure.

ACE inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.

Other conditions requiring RAAS activity.

In patients whose vascular tone and renal function primarily depend on RAAS activity (e.g., patients with severe congestive heart failure or significant renal disease, including renal artery stenosis), treatment with telmisartan and other drugs affecting the RAAS may lead to acute hypotension, hyperazotemia, oliguria, and rarely, acute renal failure (see section "Adverse reactions").

Primary hyperaldosteronism. Patients with primary hyperaldosteronism generally do not respond to antihypertensive drugs acting via blockade of the renin-angiotensin system. Therefore, telmisartan is not recommended for these patients.

Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy.

As with other vasodilators, telmisartan should be used with caution in patients diagnosed with aortic or mitral valve stenosis or obstructive hypertrophic cardiomyopathy.

Diabetic patients treated with insulin or antidiabetic medicinal products.

Hypoglycaemia may occur during treatment with telmisartan in such patients. Blood glucose levels should be monitored in these patients, and this should be considered when adjusting the dose of insulin or antidiabetic agents.

In patients with diabetes and cardiovascular risk (patients with diabetes and concomitant coronary artery disease), the risk of fatal myocardial infarction and sudden cardiovascular death may be higher when treated with antihypertensive agents such as angiotensin II receptor antagonists and ACE inhibitors. Coronary artery disease in diabetic patients may be asymptomatic and therefore undiagnosed. Diabetic patients should be carefully evaluated, e.g., by stress testing, to detect and treat concomitant coronary artery disease before initiating treatment with this medicinal product.

Hyperkalaemia. Medicinal products affecting the renin-angiotensin-aldosterone system may cause hyperkalaemia.

In elderly patients, patients with renal impairment, diabetic patients, patients receiving other medicinal products that may increase potassium levels, and/or patients with concomitant diseases, hyperkalaemia may lead to fatal outcomes.

The benefit-risk ratio must be carefully considered before combining medicinal products that inhibit the renin-angiotensin system.

Key risk factors for hyperkalaemia to consider include:

diabetes mellitus, renal impairment, age ≥70 years;
combination therapy with one or more other agents affecting the renin-angiotensin-aldosterone system, and/or potassium-containing dietary supplements. Medicinal products or therapeutic groups that may provoke hyperkalaemia include potassium-containing salt substitutes, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, non-steroidal anti-inflammatory drugs (NSAIDs, including selective COX-2 inhibitors), heparin, immunosuppressants (cyclosporine or tacrolimus), and trimethoprim;
intercurrent events, particularly dehydration, acute heart decompensation, metabolic acidosis, worsening renal function, acute worsening of kidney function (e.g., due to infections), and cellular lysis (e.g., acute limb ischaemia, acute skeletal muscle necrosis, extensive trauma).

Patients at risk require close monitoring of serum potassium concentration (see section "Interaction with other medicinal products and other forms of interaction").

Ethnic differences. As with all other angiotensin II receptor antagonists, telmisartan is less effective in reducing blood pressure in black patients compared to patients of other races. This may be explained by the higher prevalence of low-renin states in black patients with arterial hypertension.

Other. As with other antihypertensive agents, excessive reduction of blood pressure in patients with ischaemic heart disease or ischaemic cardiomyopathy may lead to myocardial infarction or stroke.

Mannitol.

The medicinal product contains mannitol. Patients with rare hereditary fructose intolerance should not take this medicinal product.

Sodium.

Each tablet contains less than 1 mmol sodium (23 mg), which is considered essentially "sodium-free".

Use during pregnancy or breastfeeding.

Pregnancy.

The medicinal product is contraindicated in pregnant women or women planning to become pregnant. If pregnancy is confirmed during treatment with this medicinal product, treatment must be discontinued immediately and, if necessary, replaced with another medicinal product approved for use during pregnancy (see sections "Contraindications" and "Special precautions for use").

There are no adequate data on the use of telmisartan in pregnant women.

Epidemiological evidence for teratogenic risk associated with ACE inhibitors during the first trimester of pregnancy has not been convincing, but a small increased risk cannot be excluded. Although there are no controlled epidemiological data on teratogenic risk with angiotensin II receptor antagonists, similar risks may exist for this class of medicinal products. When pregnancy is planned, the medicinal product should be replaced in advance with another antihypertensive agent with an established safety profile during pregnancy. Angiotensin II receptor antagonists must be discontinued immediately upon confirmation of pregnancy, and alternative treatment initiated if necessary.

It is known that use of angiotensin II receptor antagonists during the second and third trimesters of pregnancy causes foetal toxicity in humans (renal dysfunction, oligohydramnios, delayed skull ossification) and neonatal toxicity (renal failure, hypotension, hyperkalaemia). If angiotensin II receptor antagonists are used from the second trimester of pregnancy, ultrasound monitoring of foetal renal function and skull ossification is recommended. Neonates whose mothers were treated with angiotensin II receptor antagonists must be closely monitored for hypotension (see sections "Contraindications" and "Special precautions for use").

Breastfeeding.

Due to lack of information on the use of telmisartan during breastfeeding, this medicinal product is not recommended for use in breastfeeding women. Alternative treatment with a better-established safety profile is preferred, especially when breastfeeding a newborn or preterm infant.

Fertility.

Preclinical studies have not shown any effect of telmisartan on fertility in males or females.

Effects on ability to drive and use machines.

When driving or operating machinery, the possibility of dizziness or hypersomnia associated with antihypertensive therapy, including telmisartan, should be taken into account.

Dosage and Administration

Arterial Hypertension Treatment

The usual effective dose of telmisartan is 40 mg once daily. Some patients may achieve adequate blood pressure control with a daily dose of 20 mg telmisartan. If blood pressure is not adequately controlled, the dose of telmisartan may be increased to 80 mg once daily. Alternatively, telmisartan can be administered in combination with thiazide diuretics such as hydrochlorothiazide, which provide additional antihypertensive effects when used with telmisartan. When considering dose escalation, it should be noted that the maximal antihypertensive effect is achieved within 4–8 weeks of initiating treatment.

Prevention of Cardiovascular Disease

The recommended dose is 80 mg once daily. The efficacy of telmisartan at doses lower than 80 mg for cardiovascular disease prevention is unknown.

When initiating telmisartan treatment for the purpose of reducing cardiovascular risk, careful monitoring of blood pressure is recommended, and dose adjustments of other antihypertensive medications may be necessary.

Special Patient Groups

Renal Impairment. Experience with telmisartan in patients with renal insufficiency or those undergoing hemodialysis is limited. These patients should be started on the lowest initial dose of telmisartan, 20 mg (see section "Special Warnings and Precautions for Use"). Dose adjustment is not required in patients with mild to moderate renal impairment.

Hepatic Impairment. Telmisartan is contraindicated in patients with severe hepatic impairment.

In patients with mild to moderate hepatic impairment, the daily dose of telmisartan should not exceed 40 mg once daily (see section "Special Warnings and Precautions for Use").

Elderly Patients. Dose adjustment is not required.

Administration Method

TELNOR should be taken orally once daily with sufficient fluid, independent of food intake.

Tablets should be stored in the sealed blister pack to protect from moisture. Tablets should be removed from the blister immediately before administration.

Children

The safety and efficacy of TELNOR in children (under 18 years of age) have not been established.

Overdose

Information on overdose is limited.

Symptoms. The most prominent symptoms of telmisartan overdose were hypotension and tachycardia; bradycardia, dizziness, increased serum creatinine concentration, and acute renal failure have also been reported.

Treatment. Telmisartan is not removed from the body by hemodialysis. Patients should be closely monitored and receive symptomatic and supportive treatment. Management depends on the time since overdose and the severity of symptoms. Induction of emesis and/or gastric lavage may be considered. Activated charcoal may be used in the management of overdose. Serum electrolytes and creatinine levels should be monitored frequently. In case of arterial hypotension, the patient should be placed in a supine position and treated with measures aimed at rapid restoration of fluid and electrolyte volume.

Adverse Reactions

Serious adverse reactions, including anaphylactic reaction and angioedema, may occur in individual cases (frequency from ≥ 1/10,000 to <1/1,000), and acute renal failure has also been observed.

The overall frequency of adverse reactions in patients with arterial hypertension during controlled clinical trials was generally comparable between telmisartan and placebo (41.4% vs. 43.9%). The frequency of adverse reactions was independent of dose, patient sex, age, or race. The safety profile of telmisartan in patients treated for cardiovascular disease prevention corresponds to the safety profile observed in patients with arterial hypertension.

Adverse reactions are listed according to their frequency: very common (≥1/10); common (from 1/100 to <1/10); uncommon (from 1/1,000 to <1/100); rare (from 1/10,000 to <1/1,000); very rare (<1/10,000).

Within each category, adverse reactions are listed in order of decreasing severity.

Infections and infestations:

Uncommon – urinary tract infections (including cystitis), upper respiratory tract infections (including pharyngitis and sinusitis);

Rare – sepsis, including fatal cases¹.

Blood and lymphatic system disorders:

Uncommon – anaemia;

Rare – eosinophilia, thrombocytopenia.

Immune system disorders:

Rare – anaphylactic reaction, hypersensitivity.

Metabolism and nutrition disorders:

Uncommon – hyperkalaemia;

Rare – hypoglycaemia (in patients with diabetes mellitus).

Psychiatric disorders:

Uncommon – insomnia, depression;

Rare – anxiety.

Nervous system disorders:

Uncommon – syncope;

Rare – somnolence.

Eye disorders:

Rare – visual disturbance.

Ear and labyrinth disorders:

Uncommon – vertigo.

Cardiac disorders:

Uncommon – bradycardia;

Rare – tachycardia.

Vascular disorders:

Uncommon – arterial hypotension², orthostatic hypotension.

Respiratory, thoracic and mediastinal disorders:

Uncommon – dyspnoea, cough;

Very rare – interstitial lung disease⁴.

Gastrointestinal disorders:

Uncommon – abdominal pain, diarrhoea, dyspepsia, flatulence, vomiting;

Rare – dry mouth, epigastric discomfort, dysgeusia.

Hepatobiliary disorders:

Rare – liver function abnormalities/liver disorders³.

Skin and subcutaneous tissue disorders:

Uncommon – pruritus, increased sweating, rash;

Rare – angioedema (including fatal cases), eczema, erythema, urticaria, drug eruption, toxic dermatitis.

Musculoskeletal and connective tissue disorders:

Uncommon – back pain (e.g. sciatica), muscle cramps, myalgia;

Rare – arthralgia, limb pain, tendon pain (symptoms similar to tendinitis).

Renal and urinary disorders:

Uncommon – renal dysfunction, including acute renal failure.

General disorders and administration site conditions:

Uncommon – chest pain, asthenia (weakness);

Rare – influenza-like symptoms.

Investigations:

Uncommon – increased blood creatinine;

Rare – decreased haemoglobin levels, increased blood uric acid, increased liver enzymes, increased blood creatine phosphokinase.

^{1, 2, 3, 4} – See section "Adverse Reactions. Description of selected adverse reactions".

Description of selected adverse reactions

Sepsis. In the PRoFESS study, a higher incidence of sepsis was observed among patients receiving telmisartan compared to those receiving placebo. This may be due to chance or may reflect an underlying process not yet understood.

Arterial hypotension. This adverse reaction was observed commonly in patients with controlled blood pressure who received telmisartan for cardiovascular risk reduction in addition to standard therapy.

Liver function abnormalities/liver disorders. According to post-marketing data, most cases of liver function abnormalities/liver disorders occurred in patients of Japanese nationality. These patients may be more susceptible to these adverse reactions.

Interstitial lung disease. Cases of interstitial lung disease have been temporally associated with telmisartan use during post-marketing surveillance. However, a causal relationship has not been established.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after a medicinal product is authorized is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, or their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy through the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua.

Shelf life. 3 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C, in a place inaccessible to children.

Packaging. 10 tablets per blister, 1 or 3 blisters per cardboard box.

Prescription status. Prescription only.

Manufacturer.

Hetero Labs Limited.

Manufacturer's address and place of business.

Unit-V, Block V and V-A, TSIIC - Formulation SEZ, S. Nos 439, 440, 441 & 458, Polepally Village, Jadcherla Mandal, Telangana State, 509301, India.

Telnor