INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT Telmista (Telmista®)

Composition:

Active substance: telmisartan;

1 tablet contains 40 mg or 80 mg of telmisartan;

Excipients: povidone, meglumine, sodium hydroxide, lactose monohydrate, sorbitol (E 420), magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties:

40 mg tablets: oval, biconvex tablets, white to almost white;

80 mg tablets: capsule-shaped, biconvex tablets, white to almost white.

Pharmacotherapeutic group. Simple angiotensin II antagonists.

ATC code C09CA07.

Pharmacological Properties.

Pharmacodynamics.

Mechanism of Action

Telmisartan is a specific and effective oral angiotensin II receptor (AT1 subtype) antagonist. Telmisartan competitively displaces angiotensin II from its binding sites on AT1 receptors, which mediate the known actions of angiotensin II. Telmisartan has no partial agonist activity at the AT1 receptor. It selectively binds to the AT1 receptor, and this binding is long-lasting. Telmisartan has no affinity for other receptors, including AT2 and other less-characterized angiotensin receptors. The functional role of these receptors is unknown, as is the potential effect of their possible overstimulation by increased angiotensin II levels resulting from telmisartan treatment. Telmisartan reduces plasma aldosterone levels. It does not affect plasma renin levels and does not block ion channels. Telmisartan does not inhibit angiotensin-converting enzyme (kininase II), the enzyme responsible for bradykinin degradation. Therefore, bradykinin-mediated adverse effects are not expected to be enhanced.

In humans, telmisartan at a dose of 80 mg almost completely inhibits the blood pressure increase induced by angiotensin II. The blocking effect persists for 24 hours and remains evident up to 48 hours.

Clinical Efficacy and Safety

Management of Arterial Hypertension

After the first dose of telmisartan, antihypertensive activity gradually develops within 3 hours. Maximum reduction in blood pressure is achieved within 4–8 weeks of starting treatment and is maintained during long-term therapy.

The antihypertensive effect is consistently sustained over 24 hours after dosing, including the last 4 hours before the next dose, as confirmed by ambulatory blood pressure monitoring. This is supported by the ratio of telmisartan concentration just before the next dose to Cmax, which is 80% after 40 mg and 80 mg doses of telmisartan in placebo-controlled clinical trials. An expected dose-time relationship to the recovery of initial systolic blood pressure has been observed. Data regarding diastolic blood pressure are inconsistent in this context.

In patients with arterial hypertension, telmisartan reduces both systolic and diastolic blood pressure without affecting pulse rate. The contribution of the drug’s diuretic and natriuretic effects to its antihypertensive action remains to be fully elucidated. The antihypertensive efficacy of telmisartan is comparable to that of other classes of antihypertensive agents (as demonstrated in clinical trials comparing telmisartan with amlodipine, atenolol, enalapril, hydrochlorothiazide, and lisinopril).

Upon abrupt discontinuation of telmisartan, blood pressure gradually returns to pre-treatment levels over several days, with no evidence of rebound or withdrawal syndrome.

In clinical comparative studies, the incidence of dry cough was significantly lower in patients treated with telmisartan than in those receiving ACE inhibitors.

Prevention of Cardiovascular Disease

The ONTARGET study (Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial) compared the effects of telmisartan, ramipril, and their combination on cardiovascular outcomes in 25,620 patients aged 55 years or older with a history of cardiovascular disease, stroke, peripheral arterial disease, or diabetes with evidence of target organ damage (e.g., retinopathy, left ventricular hypertrophy, macro- or microalbuminuria), representing a broad population at high cardiovascular risk.

Patients were randomized to one of three treatment groups: telmisartan 80 mg, ramipril 10 mg, or combination therapy with telmisartan 80 mg and ramipril 10 mg, and were followed for a median of 4.5 years.

Telmisartan demonstrated non-inferiority to ramipril in reducing the primary composite endpoint. The incidence of the primary endpoint was similar in the telmisartan (16.7%), ramipril (16.5%), and combination therapy (16.3%) groups. The relative risk for telmisartan compared to ramipril was 1.01 (97.5% CI 0.93–1.10; p for non-inferiority = 0.0019).

All-cause mortality rates were 11.6% and 11.8% in the telmisartan and ramipril groups, respectively.

Telmisartan also demonstrated non-inferiority to ramipril in several predefined secondary endpoints, including the composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure—the primary endpoint of the HOPE trial. The relative risk of telmisartan versus ramipril for this endpoint in the ONTARGET study was 0.99 (97.5% CI 0.90–1.08; p for non-inferiority = 0.0004).

Cough and angioedema were reported less frequently in patients receiving telmisartan than in those receiving ramipril, although hypotension was reported more frequently with telmisartan.

The combination of telmisartan and ramipril did not provide additional benefit compared to either agent alone. Moreover, the combination group experienced significantly higher rates of hyperkalemia, renal dysfunction, hypotension, and dizziness. Therefore, combination therapy with telmisartan and ramipril is not recommended in this patient population.

Pharmacokinetics.

Absorption

Telmisartan is rapidly absorbed, although the extent of absorption varies. The mean absolute bioavailability of telmisartan is approximately 50%. When telmisartan is taken with food, AUC0–∞ decreases by approximately 6% (40 mg dose) to 19% (160 mg dose). Plasma concentrations 3 hours after administration are similar regardless of whether telmisartan is taken fasting or with food.

Linearity/Non-linearity

The slight reduction in AUC is not expected to result in a clinically relevant reduction in therapeutic efficacy. There is no linear relationship between dose and plasma levels. Cmax and AUC increase disproportionately with doses above 40 mg.

Distribution

Telmisartan is highly bound to plasma proteins (>99.5%), primarily to albumin and alpha-1 acid glycoprotein. The mean apparent volume of distribution at steady state (Vdss) is approximately 500 L.

Metabolism

Telmisartan undergoes metabolism primarily via conjugation of the parent substance with glucuronide. The pharmacological activity of the conjugate has not been established.

Elimination

Telmisartan exhibits biphasic pharmacokinetics with a terminal elimination half-life of >20 hours. Cmax and AUC increase disproportionately with increasing dose. There is no evidence of clinically relevant accumulation of telmisartan with repeated administration at recommended doses. Plasma concentrations are higher in women than in men, although this does not translate into a difference in clinical efficacy.

After oral administration, telmisartan is almost exclusively excreted in feces, mainly as unchanged compound. Cumulative renal excretion accounts for <1% of the dose. Total plasma clearance (Cltot) is high (approximately 1000 mL/min), compared to hepatic blood flow (approximately 1500 mL/min).

Special Patient Populations

Gender

Plasma concentrations, Cmax, and AUC were approximately 3 times and 2 times higher in women than in men, respectively.

Elderly Patients

Telmisartan pharmacokinetics are similar in patients under 65 years of age and in elderly patients.

Patients with Renal Impairment

In patients with mild, moderate, and severe renal impairment, plasma concentrations were approximately doubled. However, in dialysis-dependent patients with renal failure, plasma concentrations were low. Telmisartan is highly protein-bound in subjects with renal failure and is not dialyzable. The elimination half-life is not altered in patients with renal impairment.

Patients with Hepatic Impairment

Pharmacokinetic studies in patients with hepatic impairment showed an increase in absolute bioavailability to approximately 100%. The elimination half-life is not altered in patients with hepatic impairment.

Clinical characteristics.

Indications.

Hypertension.

Treatment of essential hypertension in adults.

Prevention of cardiovascular disease.

Reduction of cardiovascular morbidity in patients with:

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

Contraindications.

Hypersensitivity to the components of the drug;
Pregnancy or women planning to become pregnant (see section "Use during pregnancy or breastfeeding");
Obstructive biliary disorders;
Severe hepatic impairment.
Concomitant use of telmisartan and aliskiren is contraindicated in patients with diabetes mellitus or renal impairment (eGFR < 60 mL/min/1.73 m²) (see sections "Dosage and administration", "Special precautions", "Interaction with other medicinal products and other forms of interaction").

Interaction with other medicinal products and other forms of interaction.

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

Combination of telmisartan and aliskiren is contraindicated in patients with diabetes mellitus and renal impairment (eGFR < 60 mL/min/1.73 m²) and is not recommended in other patients (see sections "Contraindications", "Special precautions").

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.

Like other agents that inhibit the renin-angiotensin system, telmisartan may cause hyperkalemia (see section "Special precautions"). The risk may increase when used in combination with other agents that can also induce hyperkalemia (potassium-sparing diuretics, potassium-containing salt substitutes, potassium supplements, angiotensin-converting enzyme (ACE) 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 or potassium-containing salt substitutes. Combination with ACE inhibitors or NSAIDs is less risky provided that appropriate precautionary measures are strictly followed.

Concomitant use is not recommended.

Potassium-sparing diuretics or potassium supplements. Angiotensin II receptor antagonists such as telmisartan reduce diuretic-induced potassium loss. Potassium-sparing diuretics (e.g., spironolactone, eplerenone, triamterene, or amiloride), potassium 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, these agents should be used with caution and serum potassium levels should be monitored frequently.

Lithium. Cases of reversible increases in serum lithium concentrations and increased lithium toxicity have been reported during concomitant use of lithium with ACE inhibitors and angiotensin II receptor antagonists, including telmisartan. If combination therapy is considered necessary, serum lithium levels should be closely monitored during concomitant use.

Concomitant use requires caution.

Nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs (i.e., acetylsalicylic acid at anti-inflammatory doses, COX-2 inhibitors, and nonselective 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 impaired renal function), concomitant use of angiotensin II receptor antagonists and cyclooxygenase-inhibiting agents may lead to further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, this combination should be used with caution, especially in the elderly. Adequate hydration should be ensured, and renal function should be monitored after initiation of combination therapy and periodically thereafter.

One study reported that concomitant administration of telmisartan and ramipril resulted in a 2.5-fold increase in AUC0–24 and Cmax of ramipril and ramiprilat. The clinical significance of this observation 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 volume depletion and an increased risk of hypotension at the start of telmisartan therapy.

To 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.

Based on the pharmacological properties of baclofen and amifostine, these medicinal products may potentiate the hypotensive effect of all antihypertensive agents, including telmisartan. Additionally, alcohol, barbiturates, narcotics, or antidepressants may exacerbate orthostatic hypotension.

Systemic corticosteroids. Reduction of antihypertensive effect.

Special precautions for use.

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

Hepatic impairment. Telmista must not be administered to patients with cholestasis, obstructive biliary disorders, or severe hepatic impairment (see section "Contraindications"), as telmisartan is primarily excreted via bile. In such patients, reduced hepatic clearance of telmisartan may be expected.

Telista should be used with caution in patients with moderate to severe 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 of a single kidney when treated with drugs affecting the renin-angiotensin-aldosterone system.

Renal impairment and kidney transplantation. When Telmista is administered to patients with impaired renal function, periodic monitoring of serum potassium and creatinine levels is recommended. There is no experience with the use of Telmista in patients with recent kidney transplantation.

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

Dual blockade of the renin-angiotensin-aldosterone system.

The concomitant use of telmisartan with aliskiren in patients with diabetes mellitus or renal dysfunction (GFR < 60 ml/min/1.73 m²) is contraindicated (see section "Contraindications").

Available data indicate that concomitant use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren increases the risk of hypotension, hyperkalaemia, and deterioration of renal function (including acute renal failure). Therefore, dual blockade of the renin-angiotensin-aldosterone system by concomitant use of 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 therapy is considered absolutely necessary, it should be administered only under specialist supervision and with frequent, 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 renin-angiotensin-aldosterone system activity.

In patients in whom vascular tone and renal function depend primarily on the activity of the renin-angiotensin-aldosterone system (e.g., patients with severe congestive heart failure or significant renal disease, including renal artery stenosis), treatment with Telmista and other medicinal products affecting this system has been associated with 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 agents acting via blockade of the renin-angiotensin system. Therefore, telmisartan is not recommended for use in these patients.

Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy. As with other vasodilators, Telmista should be prescribed with particular caution in patients diagnosed with aortic stenosis, mitral valve stenosis, or obstructive hypertrophic cardiomyopathy.

Diabetic patients treated with insulin or antidiabetic medicinal products.

Hypoglycaemia may occur in such patients during treatment with telmisartan. Appropriate monitoring of blood glucose levels should be considered in these patients. Dose adjustments of insulin or antidiabetic medicinal products may be required.

In diabetic patients with cardiovascular risk (diabetic patients with 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, for example by stress testing, to detect and treat concomitant coronary artery disease before initiating treatment.

Hyperkalaemia. Hyperkalaemia may occur during treatment with medicinal products affecting the renin-angiotensin-aldosterone system.

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

The benefit-risk ratio should be carefully considered before initiating concomitant therapy with medicinal products that inhibit the renin-angiotensin system.

Key risk factors for hyperkalaemia that should be considered include:

diabetes mellitus, renal impairment, age (over 70 years);
combination therapy with one or more other agents affecting the renin-angiotensin system and/or potassium 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;
concomitant conditions, particularly dehydration, acute heart failure, metabolic acidosis, worsening renal function, sudden deterioration of kidney function (e.g., due to infections), and cellular lysis (e.g., acute limb ischaemia, rhabdomyolysis, extensive trauma).

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

Intestinal angioedema.

Cases of intestinal angioedema have been reported in patients receiving angiotensin II receptor antagonists (see section "Adverse reactions"). These patients experienced symptoms such as abdominal pain, nausea, vomiting, and diarrhoea. Symptoms resolved after discontinuation of angiotensin II receptor antagonists. If intestinal angioedema is diagnosed, the medicinal product should be discontinued and appropriate monitoring initiated until complete resolution of symptoms.

Sorbitol. The medicinal product contains sorbitol (E 420). This product should not be used by patients with rare hereditary fructose intolerance.

Lactose.

Telista contains lactose and therefore should not be used by patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.

Ethnic differences. As with all other angiotensin II receptor antagonists, telmisartan is less effective in lowering 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 hypertension.

Others. As with the use of any other antihypertensive agents, a significant reduction in blood pressure in patients with ischaemic heart disease or ischaemic cardiovascular disease may lead to myocardial infarction or stroke.

Use during pregnancy or breastfeeding.

Pregnancy.

This medicinal product is contraindicated in pregnant women or women who may 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.

Breastfeeding.

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

Fertility.

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

Ability to affect reaction speed when driving or operating machinery.

When driving vehicles or operating machinery, the possibility of dizziness or hypersomnia during antihypertensive therapy, including treatment with Telmista, should be taken into account.

Dosage and Administration

Arterial Hypertension Treatment

The usual effective dose is 40 mg once daily. Some patients may respond adequately to a daily dose of 20 mg. If the desired blood pressure is not achieved, the dose of telmisartan can be increased to 80 mg once daily. Alternatively, telmisartan may be administered in combination with thiazide diuretics such as hydrochlorothiazide, which has demonstrated additional blood pressure reduction when used concomitantly with telmisartan. When considering dose escalation, it should be noted that the maximum antihypertensive effect is generally achieved within 4–8 weeks after initiation of treatment.

Cardiovascular Risk Reduction

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

When initiating telmisartan therapy for cardiovascular risk reduction, monitoring of blood pressure is recommended, and dose adjustment of antihypertensive medications may be necessary as needed.

Special Patient Populations

Renal Impairment. Experience with telmisartan in patients with renal insufficiency or those undergoing hemodialysis is limited. Such patients should start treatment with a low dose of 20 mg (see section "Special Warnings and Precautions for Use"). Dose adjustment is not required in patients with mild to moderate renal impairment.

Concomitant use of telmisartan and aliskiren in patients with diabetes mellitus or renal impairment (GFR < 60 mL/min/1.73 m²) is contraindicated (see section "Contraindications").

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

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

Elderly Patients. No dose adjustment is necessary for elderly patients.

Administration

Telmista should be taken orally once daily with a sufficient amount of liquid, with or without food.

Telmista 40 mg tablets are not divisible and therefore are not suitable for patients who require a telmisartan dose of 20 mg for the treatment of arterial hypertension, as well as for patients with severe renal impairment or those undergoing hemodialysis. For these patients, telmisartan should be administered in an appropriate dosage form.

Pediatric Population

Telmista is not recommended for use in children under 18 years of age due to insufficient data on safety and efficacy.

Overdose

Limited information on human overdose is available.

Symptoms

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

Treatment

Telmisartan is not removed by hemodialysis. In case of overdose, close monitoring and symptomatic and supportive therapy should be instituted. The choice of treatment depends on the time elapsed since ingestion and the severity of symptoms. Measures such as induction of emesis and/or gastric lavage should be considered. Activated charcoal may be beneficial in managing overdose. Serum electrolytes and creatinine levels should be monitored frequently. In case of hypotension, the patient should be placed in a supine position and promptly administered saline replacement and fluid volume expansion.

Adverse Reactions

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

The overall incidence of adverse events in patients with arterial hypertension during controlled clinical trials receiving telmisartan was generally comparable to placebo (41.4% vs. 43.9%). The frequency of adverse events was not dose-dependent and showed no association with sex, age, or race of patients. Safety data for the drug Telzit in preventing cardiovascular diseases were consistent with data from treatment of arterial hypertension.

Adverse effects are listed below with frequency categories defined as follows: 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 effects 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 diabetic patients).

Psychiatric disorders:

Uncommon – insomnia, depression;

Rare – anxiety.

Nervous system disorders:

Uncommon – syncope;

Rare – somnolence.

Eye disorders:

Rare – vision disorders.

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, gastric discomfort.

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 resembling tendinitis).

Renal and urinary disorders:

Uncommon – renal function impairment, including acute renal failure.

General disorders:

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 indicate a process not yet understood.

Hypotension. This adverse reaction was observed commonly in patients with controlled blood pressure who were treated with telmisartan for reduction of cardiovascular disease in addition to standard therapy.

Liver function abnormalities/liver disorders. According to post-marketing data, most cases of liver function abnormalities/liver disorders were observed in patients of Japanese nationality. Patients of Japanese nationality appear to 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.

Intestinal angioedema

Cases of intestinal angioedema have been reported following administration of angiotensin II receptor antagonists (see section "Special precautions for use").

Shelf life.

3 years.

Storage conditions. Store at temperatures not exceeding 30°C.

Keep in the original packaging to protect from light.

Keep out of reach and sight of children.

Packaging. 7 tablets per blister, with 2, 4, or 8 blisters per cardboard box;

10 tablets per blister, with 3 or 6 blisters per cardboard box.

Prescription category. Prescription only.

Manufacturer.

Bulk production, primary and secondary packaging, quality control and batch release

KRKA, d.d., Novo mesto, Slovenia / KRKA, d.d., Novo mesto, Slovenia

KRKA Poland Sp. z o.o., Poland / KRKA Polska Sp. z o.o., Poland

Manufacturer's address and place of business.

Smarjeska cesta 6, 8501 Novo mesto, Slovenia / Smarjeska cesta 6, 8501 Novo mesto, Slovenia

ul. Rownolegla 5, 02-235 Warsaw, Poland / ul. Rownolegla 5, 02-235 Warsaw, Poland