Telzap® AM
The incidence of adverse reactions was determined according to the World Health Organization (WHO) classification: very common (≥1/10); often (≥1/100 and <1/10); uncommon (≥1/1000 and <1/100); rare (≥ 1/10000 and < 1/1000); very rare (< 1/10000), frequency unknown (cannot be calculated based on available data).
Potential adverse reactions during treatment with Telzap® AM include all adverse reactions that were previously reported during the use of individual components of the drug.
Adverse reactions expected based on experience with telmisartan
Serious adverse reactions include anaphylactic reactions and angioedema (incidence "rare"), and acute renal failure.
In controlled clinical trials in patients with arterial hypertension, the overall incidence of adverse reactions in the telmisartan group was generally similar to that in the placebo group (41.4% and 43.9%, respectively). The incidence of adverse reactions did not depend on the dose of the drug, nor on the gender, age or race of the patients.
The safety profile of telmisartan in patients receiving the drug to reduce cardiovascular morbidity was similar to that in patients with arterial hypertension.
The adverse reactions listed below were reported in controlled clinical trials in patients with arterial hypertension or were identified in the analysis of reports received in the post-marketing period. This list also includes serious and non-serious adverse reactions that caused treatment discontinuation in three long-term clinical studies involving 21,642 patients receiving telmisartan to reduce cardiovascular morbidity over a period of up to 6 years.
Infectious and parasitic diseases: uncommon - urinary tract infections (including cystitis), upper respiratory tract infections (including pharyngitis and sinusitis); rarely - sepsis (including death).
Disorders of the blood and lymphatic system: infrequently - anemia; rarely - eosinophilia, thrombocytopenia.
Immune system disorders: rarely - anaphylactic reactions, hypersensitivity reactions.
Metabolic and nutritional disorders: uncommon - hyperkalemia; rarely - hypoglycemia (in patients with diabetes mellitus).
Mental disorders: infrequently - insomnia, depression; rarely - anxiety.
Nervous system disorders: infrequently - fainting; rarely - drowsiness. Visual disorders: rarely - visual disturbances.
Hearing and labyrinthine disorders: uncommon - vertigo.
Cardiac disorders: infrequently - bradycardia; rarely - tachycardia.
Vascular disorders: uncommon - decreased blood pressure, orthostatic hypotension.
Disorders of the respiratory system, chest and mediastinal organs: infrequently - shortness of breath, cough; very rarely - interstitial lung disease.
Gastrointestinal disorders: uncommon - abdominal pain, diarrhea, dyspepsia, bloating, vomiting; rarely - dry mouth, discomfort in the stomach.
Disorders of the liver and biliary tract: rarely - liver dysfunction/liver damage.
Disorders of the skin and subcutaneous tissues: infrequently - itching, increased sweating, skin rash; rarely - angioedema (including fatal), eczema, erythema, urticaria, drug rash, toxicoderma.
Musculoskeletal and connective tissue disorders: uncommon - back pain (eg, sciatica), muscle spasms, myalgia; rarely - arthralgia, pain in the limbs, pain in the tendons (symptoms resembling tendonitis).
Renal and urinary tract disorders: uncommon - renal dysfunction, including acute renal failure.
General disorders and disorders at the injection site: infrequently - chest pain, asthenic syndrome (general weakness); rarely - influenza-like syndrome.
Laboratory and instrumental data: infrequently - increased concentration of creatinine in blood plasma; rarely - a decrease in the concentration of hemoglobin in the blood plasma, an increase in the concentration of uric acid in the blood plasma, an increase in the activity of liver enzymes, an increase in the concentration of creatine phosphokinase in the blood plasma.
Description of selected adverse reactions
Sepsis
In a clinical study, the incidence of sepsis in the telmisartan group was higher than in the placebo group. This may be regarded as an incidental finding or as a development of a phenomenon associated with a currently unknown mechanism.
Decreased blood pressure
This adverse reaction has often been reported in patients with controlled blood pressure while using telmisartan in combination with standard therapy to reduce cardiovascular morbidity.
Liver dysfunction/liver damage
The largest number of cases of liver dysfunction or liver damage was identified in the analysis of post-marketing case reports in patients of the Japanese ethnic group. Patients of this ethnic group are susceptible to the development of adverse reactions of this type.
Interstitial lung disease
During the post-marketing period, there have been reports of cases of interstitial lung disease that were temporarily associated with telmisartan. However, a cause-and-effect relationship between the use of telmisartan and the development of this disease has not been established.
Adverse reactions expected based on experience with amlodipine
The most common adverse reactions associated with the use of amlodipine include drowsiness, dizziness, headache, palpitations, a feeling of a “rush” of blood to the skin, abdominal pain, nausea, swelling of the ankles and other localizations, fatigue.
Disorders of the blood and lymphatic system: very rarely - leukopenia, thrombocytopenia.
Immune system disorders: very rarely - allergic reactions.
Metabolic and nutritional disorders: uncommon - weight loss, weight gain; very rarely - hyperglycemia.
Mental disorders: uncommon - insomnia, mood changes (including anxiety), depression; rarely - confusion.
Nervous system disorders: often - drowsiness, dizziness, headache (especially at the beginning of treatment); infrequently - tremor, dysgeusia, syncope, hypoesthesia, paresthesia; very rarely - hypertonicity, peripheral neuropathy; frequency unknown - extrapyramidal disorders.
Visual disorders: often - visual disturbances (including diplopia).
Hearing and labyrinthine disorders: uncommon - tinnitus.
Cardiac disorders: often - palpitations; uncommon - arrhythmia (including bradycardia, ventricular tachycardia and atrial fibrillation); very rarely - myocardial infarction.
Vascular disorders: often - a feeling of a “rush” of blood to the skin; infrequently - decreased blood pressure; very rarely - vasculitis.
Disorders of the respiratory system, chest and mediastinal organs: often - shortness of breath; infrequently - cough, rhinitis.
Gastrointestinal disorders: often - abdominal pain, nausea, irregular bowel movements (including diarrhea and constipation); infrequently - vomiting, dry oral mucosa; very rarely - pancreatitis, gastritis, gum hyperplasia.
Disorders of the liver and biliary tract: very rarely - hepatitis, jaundice, increased activity of liver enzymes (in most cases in combination with cholestasis).
Disorders of the skin and subcutaneous tissues: often - swelling of the ankles and feet; uncommon - alopecia, purpura, changes in skin pigmentation (appearance of discolored areas of the skin), increased sweating, itching, skin rash, exanthema, urticaria; very rarely - angioedema, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, photosensitivity; frequency unknown - toxic epidermal necrolysis.
Musculoskeletal and connective tissue disorders: often - muscle spasms; infrequently - arthralgia, myalgia, back pain.
Renal and urinary tract disorders: uncommon - frequent urination, dysuria, nocturia.
Disorders of the genital organs and breast: uncommon - erectile dysfunction, gynecomastia.
General disorders and disorders at the injection site: very often - swelling; often - increased fatigue, asthenic syndrome; Uncommon: chest pain, pain, general malaise.
Adverse reactions expected based on experience with amlodipine and telmisartan
Infectious and parasitic diseases: rarely - cystitis.
Mental disorders: rarely - anxiety, insomnia, depression.
Nervous system disorders: often - dizziness, infrequently - drowsiness, migraine, headache, paresthesia; rarely - fainting, peripheral neuropathy, hypesthesia, dysgeusia, tremor.
Hearing and labyrinthine disorders: uncommon - vertigo.
Cardiac disorders: uncommon - bradycardia, palpitations.
Vascular disorders: uncommon - hypotension, orthostatic hypotension, hot flashes.
Disorders of the respiratory system, chest and mediastinal organs: infrequently - cough; very rarely - interstitial lung disease.
Gastrointestinal disorders: uncommon - abdominal pain, diarrhea, nausea; rarely - vomiting, gum hypertrophy, shortness of breath, dry mouth.
Disorders of the skin and subcutaneous tissues: infrequently - itchy skin; rarely - eczema, erythema.
Musculoskeletal and connective tissue disorders: uncommon - arthralgia, muscle spasms (calf muscle cramps), myalgia; rarely - back pain, pain in the lower extremities (legs).
Urinary tract disorders: rarely - nocturia.
Disorders of the genital organs and breast: infrequently - erectile dysfunction.
General disorders and disorders at the injection site: often - peripheral edema; uncommon - asthenia, chest pain, fatigue, swelling.
Laboratory and instrumental data: infrequently - increased contransaminases; rarely - increased concentration of uric acid in the blood.
Additional information regarding the combination of amlodipine and telmisartan: Peripheral edema, a dose-related side effect of amlodipine, was observed in patients receiving the combination of amlodipine and telmisartan less frequently than in patients receiving amlodipine alone.
Telzap
Telzap tablet 40 mg x90 ATX code: C09CA07 (Telmisartan) Active substance: telmisartan Rec.INN registered by WHO
Dosage form
TELZAP®
tab. 40 mg: 30 or 90 pcs.reg. No.: LP-003545 dated 04/01/16 - Valid
Release form, composition and packaging
The tablets are almost white to yellowish in color, oblong, biconvex, scored on both sides.
1 tab.
telmisartan 40 mg
Excipients: meglumine - 12 mg, sorbitol - 162.2 mg, sodium hydroxide - 3.4 mg, povidone 25 - 20 mg, magnesium stearate - 2.4 mg.
Clinical and pharmacological group: Angiotensin II receptor antagonist Pharmacotherapeutic group: Angiotensin II receptor antagonist
pharmachologic effect
Pharmacokinetics
Indications
- essential hypertension,
- reduction in mortality and incidence of cardiovascular diseases in adult patients with cardiovascular diseases of atherothrombotic origin (coronary artery disease, stroke or a history of peripheral arterial disease) and type 2 diabetes mellitus with target organ damage.
ICD-10 codes
ICD-10 code Indication
I10 Essential [primary] hypertension
Dosage regimen
The drug is taken orally, 1 time/day, regardless of food intake, the tablets should be taken with liquid.
Arterial hypertension
The initial recommended dose of Telzap® is 40 mg (1 tablet) 1 time/day. In some patients, taking the drug at a dose of 20 mg/day may be effective. A 20 mg dose can be obtained by splitting a 40 mg tablet in half according to the score. In cases where the therapeutic effect is not achieved, the recommended dose of Telzap® can be increased to a maximum of 80 mg 1 time / day.
Alternatively, Telzap can be taken in combination with thiazide diuretics, such as hydrochlorothiazide, which have additive antihypertensive effects when used together. When deciding whether to increase the dose, it should be taken into account that the maximum antihypertensive effect is usually achieved within 4-8 weeks after the start of treatment.
Reduced mortality and incidence of cardiovascular diseases
The recommended dose of Telzap® is 80 mg 1 time/day. During the initial period of treatment, monitoring of blood pressure levels is recommended; adjustment of antihypertensive therapy may be required.
Experience with telmisartan in patients with severe renal impairment or patients on hemodialysis is limited. A lower initial dose of 20 mg/day is recommended for these patients. For patients with mild to moderate renal impairment, no dose adjustment is required.
Concomitant use of Telzap® with aliskiren is contraindicated in patients with renal failure (GFR less than 60 ml/min/1.73 m2 body surface area).
The simultaneous use of Telzap® with ACE inhibitors is contraindicated in patients with diabetic nephropathy.
For patients with mild to moderate hepatic impairment (Class A and B according to the Child-Pugh classification), the drug should be prescribed with caution; the dose should not exceed 40 mg 1 time / day. Telzap® is contraindicated in patients with severe hepatic impairment (Child-Pugh class C).
In elderly patients, no dose adjustment is required.
The use of Telzap® in children and adolescents under 18 years of age is contraindicated due to the lack of data on safety and effectiveness.
Side effect
According to WHO, undesirable effects are classified according to the frequency of their development as follows: very often (≥1/10), often (from ≥1/100 to <.1/10), infrequently (from ≥1/1000 to <.1 /100), rare (from ≥1/10,000 to <.1/1000), very rare (<.1/10,000), frequency unknown - it was not possible to determine the frequency of occurrence based on available data.
Within each group, according to frequency of occurrence, adverse reactions are presented in descending order of severity.
Infectious and parasitic diseases: infrequently - urinary tract infections, including cystitis, upper respiratory tract infections, including pharyngitis and sinusitis, rarely - sepsis, incl. with fatal outcome.
From the hematopoietic system: infrequently - anemia, rarely - eosinophilia, thrombocytopenia.
From the immune system: rarely - anaphylactic reaction, hypersensitivity.
From the side of metabolism: infrequently - hyperkalemia, rarely - hypoglycemia (in patients with diabetes mellitus).
Mental disorders: infrequently - insomnia, depression, rarely - anxiety.
From the nervous system: infrequently - fainting, rarely - drowsiness.
From the organ of vision: rarely - visual disturbances.
From the organ of hearing and labyrinthine disorders: infrequently - vertigo.
From the cardiovascular system: infrequently - bradycardia, excessive decrease in blood pressure, orthostatic hypotension, rarely - tachycardia.
From the respiratory system: infrequently - shortness of breath, cough, very rarely - interstitial lung disease.
From the gastrointestinal tract: infrequently - abdominal pain, diarrhea, dyspepsia, flatulence, vomiting, rarely - dry mouth, discomfort in the stomach, disturbance of taste.
From the liver and biliary tract: rarely - liver dysfunction/liver damage.
From the skin and subcutaneous tissues: infrequently - itching, hyperhidrosis, rash, rarely - angioedema (also fatal), eczema, erythema, urticaria, drug rash, toxic skin rash.
From the musculoskeletal system: infrequently - sciatica, muscle spasms, myalgia, rarely - arthralgia, pain in the extremities, tendinitis-like syndrome.
From the urinary system: rarely - impaired renal function, including acute renal failure.
From laboratory and instrumental studies: infrequently - an increase in the concentration of creatinine in the blood plasma, rarely - a decrease in hemoglobin content, an increase in the content of uric acid in the blood plasma, an increase in the activity of liver enzymes and CPK.
Other: infrequently - chest pain, asthenia, rarely - influenza-like syndrome.
Contraindications for use
- obstructive diseases of the biliary tract,
- severe liver dysfunction (class C according to the Child-Pugh classification),
- combined use with aliskiren in patients with diabetes mellitus or severe renal impairment (GFR less than 60 ml/min/1.73 m2 body surface area),
- simultaneous use with ACE inhibitors in patients with diabetic nephropathy,
- hereditary fructose intolerance (due to the presence of sorbitol in the composition of the drug),
- pregnancy,
- breastfeeding period,
- age under 18 years (efficacy and safety have not been established),
- hypersensitivity to the active substance or any excipients of the drug.
The drug should be prescribed with caution in case of bilateral renal artery stenosis or artery stenosis of the only functioning kidney, impaired renal function, mild and moderate liver dysfunction, decreased blood volume due to previous use of diuretics, limited salt intake, diarrhea or vomiting, hyponatremia, hyperkalemia, condition after kidney transplantation (no experience with use), severe chronic heart failure, aortic and mitral valve stenosis, hypertrophic obstructive cardiomyopathy, primary hyperaldosteronism (efficacy and safety have not been established), patients of the Negroid race.
Use during pregnancy and breastfeeding
Currently, there is no reliable information on the safety of telmisartan in pregnant women. In animal studies, reproductive toxicity of the drug was revealed. The use of Telzap® is contraindicated during pregnancy.
If long-term treatment with Telzap® is necessary, patients planning pregnancy should select an alternative antihypertensive drug with a proven safety profile for use during pregnancy. Once pregnancy is established, treatment with Telzap® should be stopped immediately and, if necessary, alternative treatment should be started.
As shown by the results of clinical observations, the use of angiotensin II receptor antagonists in the second and third trimesters of pregnancy has a toxic effect on the fetus (deterioration of renal function, oligohydramnios, delayed skull ossification) and the newborn (renal failure, arterial hypotension and hyperkalemia). When using angiotensin II receptor antagonists in the second trimester of pregnancy, ultrasound of the fetal kidneys and skull is recommended. Children whose mothers took angiotensin II receptor antagonists during pregnancy should be closely monitored for hypotension.
There is no information on the use of telmisartan during breastfeeding. The use of Telzap® during breastfeeding is contraindicated. An alternative antihypertensive drug with a more favorable safety profile should be used, especially when feeding a newborn or premature infant.
Use for liver dysfunction
The use of the drug is contraindicated for obstructive diseases of the biliary tract, severe liver dysfunction (class C according to the Child-Pugh classification).
The drug should be prescribed with caution for mild to moderate liver dysfunction.
Use for impaired renal function The drug should be prescribed with caution in cases of bilateral renal artery stenosis or stenosis of the artery of the only functioning kidney, impaired renal function, or the condition after kidney transplantation (no experience with use).
Use in children The use of the drug is contraindicated in people under 18 years of age (efficacy and safety have not been established).
Use in elderly patients No dose adjustment is required in elderly patients.
special instructions
Liver dysfunction
The use of Telzap® is contraindicated in patients with cholestasis, biliary obstruction or severe liver dysfunction (Child-Pugh class C), since telmisartan is mainly excreted in the bile. It is assumed that in such patients the hepatic clearance of telmisartan is reduced. In patients with mild or moderate liver dysfunction (Child-Pugh class A and B), Telzap® should be used with caution.
Renovascular hypertension
When treated with drugs that act on the RAAS, the risk of severe arterial hypotension and renal failure increases in patients with bilateral renal artery stenosis or arterial stenosis of a single functioning kidney.
Renal dysfunction and kidney transplantation
When using Telzap® in patients with impaired renal function, periodic monitoring of potassium and creatinine levels in the blood plasma is recommended. There is no clinical experience with the use of Telzap® in patients who have recently undergone kidney transplantation.
Decrease in BCC
Symptomatic arterial hypotension, especially after the first dose of Telzap®, may occur in patients with low blood volume and/or sodium content in the blood plasma due to previous treatment with diuretics, restriction of salt intake, diarrhea or vomiting. Such conditions (fluid and/or sodium deficiency) should be eliminated before starting Telzap®.
Double blockade of the RAAS
Concomitant use of telmisartan with aliskiren is contraindicated in patients with diabetes mellitus or renal failure (GFR less than 60 ml/min/1.73 m2 body surface area).
The simultaneous use of telmisartan and ACE inhibitors is contraindicated in patients with diabetic nephropathy.
As a result of inhibition of the RAAS, arterial hypotension, syncope, hyperkalemia and impaired renal function (including acute renal failure) have been observed in predisposed patients, especially when combined with several drugs that also act on this system. Therefore, double blockade of the RAAS (for example, while taking telmisartan with other RAAS antagonists) is not recommended.
In cases where vascular tone and renal function depend primarily on the activity of the RAAS (for example, in patients with chronic heart failure or kidney disease, including renal artery stenosis or stenosis of the artery of a single kidney), the prescription of drugs that affect this system may be accompanied by the development of acute arterial hypotension, hyperazotemia, oliguria, and in rare cases, acute renal failure.
Primary hyperaldosteronism
In patients with primary hyperaldosteronism, treatment with antihypertensive drugs that act by inhibiting the RAAS is usually ineffective. In this regard, the use of Telzap® is not recommended.
Stenosis of the aortic and mitral valves, hypertrophic obstructive cardiomyopathy
As with other vasodilators, patients with aortic or mitral stenosis, as well as hypertrophic obstructive cardiomyopathy, should be especially careful when using Telzap®.
Patients with diabetes mellitus receiving insulin or oral hypoglycemic agents
During treatment with Telzap®, hypoglycemia may occur in such patients. Glycemic control should be strengthened, because It may be necessary to adjust the dose of insulin or hypoglycemic agent.
Hyperkalemia
The use of drugs acting on the RAAS can cause hyperkalemia. In elderly patients, patients with renal failure or diabetes mellitus, patients taking medications that increase plasma potassium levels, and/or patients with underlying medical conditions, hyperkalemia can be fatal.
When deciding on the concomitant use of drugs acting on the RAAS, it is necessary to assess the risk-benefit ratio. The main risk factors for hyperkalemia that should be considered are:
- diabetes mellitus, renal failure, age (patients over 70 years old),
- combination with one or more drugs acting on the RAAS and/or potassium-containing nutritional supplements. Drugs or therapeutic classes of drugs that can cause hyperkalemia include potassium-containing salt substitutes, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, NSAIDs (including selective COX-2 inhibitors), heparin, immunosuppressants (cyclosporine or tacrolimus) and trimethoprim,
- intercurrent diseases, especially dehydration, acute heart failure, metabolic acidosis, renal dysfunction, cytolysis syndrome (for example, acute limb ischemia, rhabdomyolysis, major trauma).
Patients at risk are advised to carefully monitor plasma potassium levels.
Sorbitol
Telzap® contains sorbitol (E420). Patients with rare hereditary fructose intolerance should not take the drug.
Ethnic differences
As noted for ACE inhibitors, telmisartan 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 these patient populations.
Other
As with the use of other antihypertensive drugs, an excessive decrease in blood pressure in patients with ischemic cardiomyopathy or coronary artery disease can lead to the development of myocardial infarction or stroke.
Impact on the ability to drive vehicles and operate machinery
No special clinical studies have been conducted to study the effect of the drug on the ability to drive a car or use machinery. When driving a car and working with mechanisms that require increased concentration, you should be careful, because During the use of Telzap®, dizziness and drowsiness may rarely occur.
Overdose
Symptoms: The most pronounced manifestations of overdose were an excessive decrease in blood pressure and tachycardia, and bradycardia, dizziness, increased serum creatinine concentrations and acute renal failure were also reported.
Treatment: Patients should be carefully monitored and treated symptomatically as well as supportively. The treatment approach depends on the time elapsed after taking the drug and the severity of symptoms. Recommended measures include inducing vomiting and/or gastric lavage; it is advisable to take activated charcoal. Plasma electrolytes and creatinine levels should be regularly monitored. If blood pressure decreases excessively, the patient should take a horizontal position with his legs elevated, and it is necessary to quickly replenish the blood volume and the lack of electrolytes. Telmisartan is not eliminated by hemodialysis.
Drug interactions
Double blockade of the RAAS
Concomitant use of telmisartan with aliskiren is contraindicated in patients with diabetes mellitus or renal failure (GFR less than 60 ml/min/1.73 m2 body surface area) and is not recommended in other patients.
The simultaneous use of telmisartan and ACE inhibitors is contraindicated in patients with diabetic nephropathy.
Data from clinical studies have shown that dual blockade of the RAAS due to the combined use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren is associated with an increased incidence of adverse events such as hypotension, hyperkalemia and renal dysfunction (including acute renal failure) compared with the use of only one a drug acting on the RAAS.
Hyperkalemia
The risk of developing hyperkalemia may be increased when used concomitantly with other drugs that can cause hyperkalemia (potassium-containing dietary supplements and salt substitutes containing potassium, potassium-sparing diuretics (for example, spironolactone, eplerenone, triamterene or amiloride), NSAIDs (including selective COX-2 inhibitors) , heparin, immunosuppressants (cyclosporine or tacrolimus) and trimethoprim). If necessary, against the background of documented hypokalemia, the combined use of drugs should be carried out with caution and the potassium content in the blood plasma should be regularly monitored.
Digoxin
When telmisartan was co-administered with digoxin, an average increase in plasma digoxin Cmax by 49% and Cmin by 20% was noted. At the beginning of treatment, when selecting a dose and stopping treatment with telmisartan, the concentration of digoxin in the blood plasma should be carefully monitored to maintain it within the therapeutic range.
Potassium-sparing diuretics or potassium supplements
Angiotensin II receptor antagonists, such as telmisartan, reduce diuretic-induced potassium loss. Potassium-sparing diuretics (eg, spironolactone, eplerenone, triamterene, or amiloride), potassium-containing dietary supplements, or salt substitutes may lead to significant increases in plasma potassium levels. If concomitant use is indicated because hypokalemia is documented, they should be used with caution and in conjunction with regular monitoring of plasma potassium levels.
Lithium preparations
When lithium preparations were used together with ACE inhibitors and angiotensin II receptor antagonists, including telmisartan, a reversible increase in the concentration of lithium in the blood plasma and its toxic effect occurred. If it is necessary to use this combination of drugs, it is recommended to carefully monitor lithium concentrations in the blood plasma.
NSAIDs
NSAIDs (i.e., acetylsalicylic acid at doses used for anti-inflammatory treatment, COX-2 inhibitors and non-selective NSAIDs) may reduce the antihypertensive effect of angiotensin II receptor antagonists. In some patients with impaired renal function (eg, dehydrated patients, elderly patients with impaired renal function), concomitant use of angiotensin II receptor antagonists and drugs that inhibit COX-2 may lead to further deterioration of renal function, including the development of acute renal failure, which , as a rule, is reversible. Therefore, the combined use of drugs should be done with caution, especially in elderly patients. Adequate fluid intake should be ensured and renal function should be monitored at the start of co-administration and periodically thereafter.
Diuretics (thiazide or loop)
Previous treatment with high-dose diuretics, such as furosemide (loop diuretic) and hydrochlorothiazide (thiazide diuretic), may lead to hypovolemia and the risk of hypotension when starting treatment with telmisartan.
Other antihypertensive drugs
The effect of telmisartan may be enhanced by concomitant use of other antihypertensive drugs.
Based on the pharmacological properties of baclofen and amifostine, it can be assumed that they will enhance the therapeutic effect of all antihypertensive drugs, including telmisartan. In addition, orthostatic hypotension may be exacerbated by the use of ethanol, barbiturates, narcotics, or antidepressants.
Corticosteroids (for systemic use)
Corticosteroids weaken the effect of telmisartan.
Conditions and periods of storage The drug should be stored out of the reach of children at a temperature not exceeding 25°C. Shelf life: 2 years.
Conditions for dispensing from pharmacies The drug is dispensed with a prescription.
Telzap Plus 40 mg/12.5 mg No. 30 tablet.
APPROVED by the Order of the Chairman of the Committee for Control of Medical and Pharmaceutical Activities of the Ministry of Health and Social Development of the Republic of Kazakhstan Instructions for the medical use of the drug Telzap Plus Trade name Telzap Plus International nonproprietary name No Dosage form Tablets 40 mg/12.5 mg; 80 mg/12.5 mg; 80 mg/25 mg Composition One tablet contains active substances: telmisartan 40,000 or 80,000 mg, respectively, hydrochlorothiazide 12,500 mg or 25,000 mg, respectively, excipients: sorbitol, sodium hydroxide, povidone 25, magnesium stearate Description Oblong tablets with a biconvex surface from white to yellowish in color, with the number “41” embossed on one side of the tablet, about 12 mm long, about 6 mm wide (for a dosage of 40 mg/12.5 mg). Tablets are oblong in shape with a biconvex surface, white to yellowish in color, with the number “81” embossed on one side of the tablet, about 16.5 mm long, about 8.3 mm wide (for a dosage of 80 mg/12.5 mg). Tablets are oblong in shape with a biconvex surface, white to yellowish in color, with the number “82” embossed on one side of the tablet, about 16 mm long, about 8 mm wide (for a dosage of 80 mg/25 mg). Pharmacotherapeutic group Drugs affecting the renin-angiotensin system, angiotensin II antagonists with diuretics. Telmisartan and diuretics ATC code C09DA07 Pharmacological properties Pharmacokinetics The simultaneous use of hydrochlorothiazide and telmisartan does not affect the pharmacokinetics of these drugs. Absorption of Telmisartan: After oral administration, peak concentrations of telmisartan are reached after 0.5 - 1.5 hours. The absolute bioavailability of telmisartan at a dose of 40 mg and 160 mg is 42% and 58%, respectively. When telmisartan is taken simultaneously with food, the reduction in AUC (area under the concentration-time curve) ranges from 6% (at a dose of 40 mg) to 19% (at a dose of 160 mg). 3 hours after administration, the concentration in the blood plasma levels off, regardless of food intake. A slight decrease in AUC does not cause a decrease in therapeutic efficacy. The pharmacokinetics of oral telmisartan is nonlinear at doses of 20–160 mg, with a more than proportional increase in plasma concentrations (Cmax and AUC) with increasing dose. No clinically significant accumulation of telmisartan was detected. Hydrochlorothiazide: After oral administration of Telzap Plus, peak concentrations of hydrochlorothiazide are achieved approximately 1.0 - 3.0 hours after dosing. Based on cumulative renal excretion of hydrochlorothiazide, absolute bioavailability is approximately 60%. Distribution Telmisartan is highly bound to plasma proteins (more than 99.5%), mainly to albumin and alpha-1-acid glycoprotein. The volume of distribution is approximately 500 L, indicating additional tissue binding. Hydrochlorothiazide is 68% bound to plasma proteins and the volume of distribution is 0.83 - 1.14 l/kg. Biotransformation Telmisartan is metabolized by conjugation to form a pharmacologically inactive acyl glucuronide. The glucuronide of the parent compound is the only metabolite that has been identified in humans. Following a single dose of 14C-labeled telmisartan, glucuronide accounts for approximately 11% of the measured radioactivity in plasma. Cytochrome P450 and isoenzymes are not involved in the metabolism of telmisartan. Hydrochlorothiazide is not metabolized in humans. Elimination Telmisartan: Following intravenous or oral administration of 14C-labeled telmisartan, the majority of the administered dose (>97%) is eliminated in the feces via biliary excretion. Small amounts were found in the urine. The total plasma clearance of telmisartan after oral administration is > 1500 ml/min. The terminal half-life is >20 hours. Hydrochlorothiazide is excreted almost completely unchanged in the urine. About 60% of an oral dose is eliminated within 48 hours. Renal clearance is about 250 - 300 ml/min. The terminal half-life is 10 - 15 hours. Special Populations Elderly Patients The pharmacokinetics of telmisartan do not differ between the elderly and patients under 65 years of age. Gender Plasma concentrations of telmisartan are 2-3 times higher in women than in men. In clinical studies, there was no significant increase in blood pressure response or the incidence of orthostatic hypotension in women. No dose adjustment is required. There was a trend towards higher plasma concentrations of hydrochlorothiazide in women than in men. This has no clinical significance. Patients with renal impairment Renal excretion does not affect the clearance of telmisartan. Based on the results of limited experience with the use of Telzap Plus in patients with mild to moderate renal impairment (creatinine clearance 30 - 60 ml/min, average value about 50 ml/min), dose adjustment is not necessary in patients with reduced renal function. Telmisartan is not removed from the blood by hemodialysis. In patients with impaired renal function, the rate of elimination of hydrochlorothiazide is reduced. In a study in patients with an average creatinine clearance of 90 ml/min, the half-life of hydrochlorothiazide was increased. In patients with a nonfunctional kidney, the half-life is approximately 34 hours. Patients with hepatic impairment In patients with hepatic impairment, the absolute bioavailability of telmisartan increases to 100%. The half-life does not change in liver failure. Pharmacodynamics Telzap Plus is a combination of an angiotensin II receptor antagonist (ARAII), telmisartan, and a thiazide diuretic, hydrochlorothiazide. The combination of these components has an additive antihypertensive effect, reducing blood pressure to a greater extent than each component alone. Telzap Plus, when taken once a day, leads to an effective and gradual decrease in blood pressure. Telmisartan is an effective and specific (selective) angiotensin II receptor (AT1 type) antagonist for oral administration. Telmisartan displaces angiotensin II with very high affinity from its binding sites in receptor subtype 1 (AT1), which is responsible for the known actions of angiotensin II. Telmisartan does not exhibit any partial agonist activity at the AT1 receptor. Telmisartan selectively binds to the AT1 receptor. The bond is long lasting. Telmisartan does not show affinity for other receptors, including the AT2 receptor and other less studied AT receptors. The functional significance of these receptors, as well as the effect of their possible excessive stimulation by angiotensin II, the concentration of which increases with the administration of telmisartan, have not been studied. Telmisartan reduces plasma aldosterone levels and does not block human plasma renin or ion channels. Telmisartan does not inhibit angiotensin-converting enzyme (kinase II), which reduces the production of bradykinin. Therefore, there is no increase in side effects associated with bradykinin. An 80 mg dose of telmisartan administered to healthy volunteers almost completely inhibits the increase in blood pressure caused by angiotensin II. The inhibitory effect lasts for more than 24 hours (up to 48 hours). After taking the first dose of telmisartan, blood pressure decreases after 3 hours. The maximum reduction in blood pressure is usually achieved 4-8 weeks after the start of treatment and is maintained during long-term therapy. The hypotensive effect continues for 24 hours after taking the drug, including 4 hours before taking the next dose, as confirmed by blood pressure measurements, as well as outpatient stable (above 80%) ratio of the minimum and maximum concentrations of the drug after taking 40 and 80 mg of telmisartan in placebo-controlled clinical studies. In patients with hypertension, telmisartan reduces both systolic and diastolic blood pressure without affecting heart rate. The antihypertensive efficacy of telmisartan is comparable to other classes of antihypertensive drugs (as shown in clinical studies comparing telmisartan with amlodipine, atenolol, enalapril, hydrochlorothiazide and lisinopril). In a double-blind, controlled clinical trial (N = 687 patients assessed for efficacy) in subjects not responding to the 80 mg/12.5 mg combination, a gradual blood pressure lowering effect of the 80 mg/25 mg combination was demonstrated compared with long-term treatment with the 80 mg/25 mg combination. 80 mg/12.5 mg 2.7/1.6 mmHg. (SBP/DBP) (difference in adjusted mean change from baseline). In the study with the 80 mg/25 mg combination, blood pressure decreased, resulting in an overall decrease of 11.5/9.9 mmHg. (GARDEN/DBP). In a pooled analysis of two similar 8-week, double-blind, placebo-controlled clinical trials comparing valsartan/hydrochlorothiazide 160 mg/25 mg (N = 2121 patients assessed for efficacy), a greater blood pressure lowering effect of 2.2/1.2 mmHg was observed. . (SBP/DBP) (adjusted mean change from baseline, respectively) in favor of telmisartan/hydrochlorothiazide 80 mg/25 mg. After abrupt cessation of telmisartan treatment, blood pressure gradually returns to the initial value over several days without signs of rebound hypertension. In clinical trials directly comparing the two treatments, the incidence of dry cough was significantly lower in patients receiving telmisartan than in those receiving angiotensin-converting enzyme inhibitors. In patients who had recently had a stroke, there was an increased incidence of sepsis with telmisartan compared with placebo, 0.70% versus 0.49% [RR 1.43 (95% confidence interval 1.00 to 2.06)], incidence deaths from sepsis were higher in patients taking telmisartan (0.33%) compared with patients taking placebo (0.16%) [HR 2.07 (95% confidence interval 1.14 - 3.76)] . The observed increase in the incidence of sepsis associated with the use of telmisartan may be either a coincidental event or may be due to a mechanism that is currently unknown. The effects of telmisartan on mortality and cardiovascular morbidity are currently unknown. Hydrochlorothiazide is a thiazide diuretic. The mechanism of the antihypertensive effect of thiazide diuretics is not fully known. Thiazides affect the renal tubular reabsorption mechanisms of electrolytes, directly increasing the excretion of sodium and chloride by approximately equivalent amounts. The diuretic effect of hydrochlorothiazide reduces plasma volume, increases plasma renin activity, increases aldosterone secretion with a subsequent increase in urinary potassium, loss of bicarbonate and a decrease in serum potassium. Presumably through blockade of the renin-angiotensin-aldosterone system, co-administration of telmisartan tends to prevent potassium loss associated with these diuretics. When using hydrochlorothiazide, the onset of diuresis occurs after 2 hours, and the peak effect occurs after approximately 4 hours, while the effect persists for approximately 6-12 hours. Epidemiological studies have shown that long-term treatment with hydrochlorothiazide reduces the risk of cardiovascular mortality and morbidity. Indications for use - treatment of essential arterial hypertension (in case of ineffectiveness of telmisartan or hydrochlorothiazide as monotherapy) Method of administration and doses Adults Telzap Plus tablets are intended for oral use, regardless of food intake, taken once a day and should be washed down with water. Telzap Plus is indicated for patients whose blood pressure is not adequately controlled on telmisartan monotherapy. Individual dose titration of each of the two components is recommended before switching to a fixed dose combination. If clinically appropriate, direct conversion from monotherapy to a fixed combination may be considered. Telzap Plus 40 mg/12.5 mg can be taken once daily in patients whose blood pressure is not adequately controlled by telmisartan 40 mg monotherapy. Telzap Plus 80 mg/12.5 mg can be taken once daily in patients whose blood pressure is not adequately controlled by telmisartan 80 mg monotherapy. Telzap Plus 80 mg/25 mg may be administered once daily in patients whose blood pressure is not adequately controlled on Telzap Plus 80/12.5 mg or in patients whose blood pressure has previously been stabilized on telmisartan and hydrochlorothiazide alone. Use in the elderly No dose adjustment is required. Patients with renal insufficiency Periodic monitoring of renal function is recommended (see section "Special Instructions") Patients with hepatic insufficiency In patients with mild to moderate hepatic insufficiency, the dosage should not exceed Telzap Plus 40 mg/12.5 mg once daily. Telzap Plus is not indicated for patients with severe liver dysfunction. Thiazides should be used with caution in patients with impaired liver function (see section "Special Instructions"). Children The safety and effectiveness of Telzap Plus in children and adolescents under 18 years of age has not been established. Data not available. Side effects The overall incidence of adverse events with Telzap Plus was comparable to that with telmisartan monotherapy in a series of studies involving 1471 patients receiving a combination of telmisartan and hydrochlorothiazide (835) or telmisartan alone (636). Adverse events were not dose dependent and were not related to the patient's gender, age, or race. ADVERSE EVENTS OBSERVED DURING CLINICAL STUDIES WITH THE COMBINATION OF TELMISARTAN AND HYDROCHLORTHIAZIDE ARE LISTED BELOW USING THE FOLLOWING CLASSIFICATION: VERY COMMON (≥ 1/10); COMMON (≥ 1/100 TO <1/10); INCREASED (≥ 1/1000 TO ≤ 1/100); RARE (≥ 1/10,000 TO ≤ 1/1000), VERY RARE (≤ 1/10,000); UNKNOWN (ASSESSMENT NOT POSSIBLE BASED ON AVAILABLE DATA). OFTEN - Dizziness INCOMMEN - HYPOKALEMIA - FEELINGS OF RESTlessness, ANXIETY - SWONING, PARESTHESIA - Dizziness (HEARING AND VESTIBULAR DISORDERS) - TACHYCARDIA, ARRHYTHMIA - HYPOTENSION, ORTHOSTATIC HYPOTENSION - DYSPHERE - DIARRHEA, FUTELLENCE, DRY MOUTH - BACK PAIN , MUSCLE SPAMS, MYALGIA - ERECTILE DYSFUNCTION - CHEST PAIN - INCREASED URIC ACID LEVELS IN THE BLOOD RARE - Quincke's edema (POSSIBLY FATAL), ERYTHEMA, ITCHING, RASH, SWEATING, HURTICS - BRONCHITIS, FAR INGIT, SINUSITIS - EXCERNSATION OR ACTIVATION OF SYSTEMIC RED LUPUS (BASED ON POST-MARKETING EXPERIENCE) - HYPERURICEMIA, HYPONATREMIA - DEPRESSION - INSOMNIA, SLEEP DISTURBANCE - VISUAL DISORDER, BLURRY VISION - RESPIRATORY FAILURE (INCLUDING PNEUMONIA AND PULMONARY EDEMA) - ABDOMINAL PAIN, CONSTIPATION, DYSPEPSIA, VOMITING, GASTRITIS - ARTHALGIA, MUSCULAR CONVISIONS, PAIN IN THE LIMB - ABNORMAL DISORDERS OF LIVER FUNCTION (SEE SECTION “DESCRIPTION OF SPECIFIC ADVERSE REACTIONS”) - FLU-LIKE CONDITION - INCREASED LEVELS OF CRATININE, CREATINE PHOSPHOKINASE, LIVER ENZYMES ADDITIONAL IN ADVERSE REACTIONS PREVIOUSLY REPORTED FOR INDIVIDUAL COMPONENTS OF THE COMBINATION DRUG MAY THERE ARE POTENTIAL ADVERSE REACTIONS WHEN USING TELZAP PLUS, EVEN IF THEY ARE NOT OBSERVED IN CLINICAL STUDIES OF THIS COMBINATION DRUG. TELMISARTAN: ADVERSE REACTIONS OCCURRED WITH THE SAME FREQUENCY IN PATIENTS WHO RECEIVED PLACEBO AND TELMISARTAN. IN PLACEBO-CONTROLLED STUDIES, THE OVERALL INCIDENCE OF ADVERSE REACTIONS WITH TELMISARTAN (41.4%) WAS USUALLY COMPARABLE TO PLACEBO (43.9%). The following adverse reactions listed below were obtained from all clinical studies in patients who received telmisartan for hypertension or in patients over 50 with a high risk of cardiovascular events. INCOMMEN - UPPER RESPIRATORY TRACT INFECTIONS, URINARY TRACT INFECTIONS, INCLUDING CYSTITIS - ANEMIA - HYPERKALEMIA - BRADYCARDIA - COUGH - RENAL FAILURE (INCLUDING ACUTE RENAL FAILURE) - ASTHENIA RARE - SEPSIS IN T NUMBER OF FATAL RESULTS (SEE SECTION “DESCRIPTION OF SELECTED ADVERSE REACTIONS") - EOSINOPHILIA, THROMBOCYTOPENIA - INCREASED SENSITIVITY, ANAPHYLACTIC REACTIONS - HYPOGLYCEMIA (IN PATIENTS WITH DIABETES MELLITUS) - Drowsiness - DISCOMFORT IN THE STOMACH AREA - ECZEMA, DRUG SLEEP PI, TOXIC RASHE - ARTHROSIS, TENDON PAIN - HEMOGLOBIN LEVELS GREATLY REDUCED Rarely - interstitial lung disease (see section “Description of individual adverse reactions”) Hydrochlorotiazide: can cause or aggravate hypovolemia, which can lead to electrolyte imbalance (see the “Special Instructions” section) The frequency is not known - sialadenitis - aplastic anemia, hemolytic anemia , Lack of bone marrow, leukopenia, neutropenia, agranulocytosis, thrombocytopenia - anaphylactic reactions, hypersensitivity - unconditional diabetes mellitus - anorexia, decrease in appetite, electrolyte imbalance, hypercholesterolemia, hyperglycemia - anxiety, dizziness - nonsense, oxantic cupboard, obscure cloth -angled Glaucoma - necrotic vasculitis -pancreatitis, discomfort in the stomach-hepatocellular jaundice, cholestatic jaundice-lupid-like syndrome, photosensitization, vasculitis of the skin, toxic epidermal necrolysis-weakness-interstitial nephritis, renal dysfunction, glucosuria-hyperthermia-increased level of triglycerides. In most cases, a liver disorders impaired liver function/liver disorder from post-marketing experience with telmisartan arose in patients from Japan. Residents of Japan are most likely to have these adverse reactions. Sepsis in the Profess study, an increase in the frequency of sepsis cases was observed in the Telmisartan treatment group compared to placebo. The phenomenon can be random or associated with a mechanism that is currently not known (see the section "Pharmacodynamics"). Interstitial diseases of the lungs of interstitial lung lesions were registered during post -marketing outlets using telmisartan. Nevertheless, the causal relationship was not established. Reporting on suspected adverse reactions reports on alleged adverse reactions allows you to continue monitoring the benefit of the benefit/risk of the drug. Medical workers must report any alleged adverse reactions. Contraindications - increased sensitivity to active substances or to any of the excipients - increased sensitivity to other sulfonamid -containing substances (since hydrochlorolertiazide is sulfonamide -containing drug) - II and III trimetra of pregnancy and the period of lactation - cholestasis and obstructive diseases of the biliary tracts - impaired liver function - impaired liver function Severe renal failure (creatinine clearance <30 ml/ min) - stable hypokalemia, hypercalcemia - joint intake with aliskirene in patients with diabetes or renal failure (SKF <60 ml/ min/ 1.73 m2) - hereditary fructose intolerance, galactose ( Galactocuria)-children and adolescence up to 18 years of age of medicinal interactions of lithium, a reversible increase in lithium concentration in blood and toxication was registered during the concomitant purpose of lithium with angiotensin-monitoring enzyme inhibitors. Rare cases have also been reported when using antagonists of angiotensin II receptors (including Telzap Plus). The simultaneous use of lithium and telzap plus is not recommended (see section “Special Instructions”). If this combination is necessary, it is recommended to carry out thorough monitoring of the level of serum lithium during treatment. Medicines that cause potassium loss and hypokalemia (for example, other potassium diuretic, laxatives, corticosteroids, ACTH, amphotericin, carbenoksolon, Penicillin G Sodium, Salicylic acid and its derivatives) When prescribing these drugs with a combination of hydrochlortiazid-telmisartan, monitoring of the level of potassium in the level of potassium in Blood. These drugs can enhance the effect of hydrochlorotiazide on the level of potassium in the blood serum (see section “Special Instructions”). Medicines that increase the level of potassium in the blood and cause hyperkalemia (for example, ACE inhibitors, calisbring diuretics, potassium additives containing potassium, cyclosporin or other drugs such as sodium heparin). If these drugs are prescribed simultaneously with the combination of hydrochlorortiazide-telmisartan, monitoring of the level of potassium in the blood is recommended. Based on the experience of using other drugs inhibiting the Renin-angienzin system, the simultaneous use of the above drugs can lead to an increase in the level of potassium in serum and, therefore, is not recommended for use (see the “Special Instruction” section). Medicines that respond to changes in the level of potassium in serum periodic control of potassium levels in the blood serum and ECG are recommended when prescribing a telzap plus with drugs responding to changes in potassium in blood serum (for example, cardiac glycosides, antiarrhythmic drugs), as well as with drugs) Preparations inducing the trembling and flickering of ventricles (for example, some antiarrhythmic agents), while hypokalemia is a predisposing factor to trembling and flickering ventricles. - Antiarrhythmic drugs of class IA (for example, quinidine, hydrochinidine, dysopiramide) - antiarrhythmic drugs of class III (for example, amiodarone, sotalol, prefhylaid, ibulaid) - some antipsychotic drugs (for example, thioridazine, chlorpromazine, levomepromazin, trifluopezine, cymemazine, sulpiride, sultopris Amisavavid, tiapid, pimoside, haloperidol, drooperidol) - other drugs (for example, Bephidil, cisapride, dipemanil, erythromycin IV, halophane, mizolastine, pentamidine, sparfloxacin, terphenin, vincamine IV) heart glycosides of hypokalemia or hypomagnesia, induced by thiazids, method of method. CHIRTMENTMENT , Induced by cardiac glycosides (see section "Special instructions"). Other antihypertensive agents of telmisartan can increase the hypotensive effect of other hypertension drugs. Invodiabetic drugs (oral drugs and insulin) may require the regulation of dosage of antiabetic drugs (see the section “Special Instructions”). Metformin Metformin should be used with caution. The risk of lactoacidosis, induced by a possible functional renal failure associated with hydrochlorotiazide. Holestyramine and collaxual resins of hydrochlorotiazide absorption are disrupted in the presence of anion metabolic resin. Non-steroidal anti-inflammatory drugs of the NSAID (i.e. acetylsalicylic acid when used in anti-inflammatory schemes, TSOG-2 inhibitors and non-? Non-selective NSAIDs) can reduce diuretic, sodium and antihypertensive effects of thiazide diuretics and antihypertensive effects of angiotensin receptor II. In some patients with impaired renal function (for example, in patients with dehydration or elderly patients with impaired renal function), the joint administration of angiotensin II receptors and drugs that inhibit cyclooxygenase can lead to further deterioration of renal function, including possible acute renal failure Which is usually reversible. Therefore, the combination should be carried out with caution, especially in elderly patients. Patients should take a sufficient amount of fluid, and it is necessary to constantly pay attention to monitoring of the kidney function after the onset of concomitant therapy and periodically in the next period of time. Ramipril in one study the joint use of telmisartan and ramipril led to an increase of 2.5 times AUC0-24 and CMACS Ramipril and Ramiprilat. The clinical significance of this observation is not known. Pressor amines (for example, norepinephrine) a decrease in the effect of pressor amines. Forgeable relaxants of the skeletal muscles (for example, tubocurine), the potentiation of the effect of non -tracing relaxants of the drugs used in the treatment of gout (for example, probenecide, sulfinpirazone and allopurinol), the dose of uricosuric drugs can be necessary, since hydrochlorotiazide can increase the level Blood. An increase in the dose of probenecide or sulfinpirazone may be necessary. The simultaneous purpose of thiazide diuretics can increase the frequency of hypersensitivity reactions to allopurinol. Calcium salts thiazide diuretics can increase the level of calcium in the blood serum due to a decrease in their excretion. If it is necessary to prescribe calcium, it should be controlled by its level in the blood and, accordingly, adjust the dose. Beta blockers and diazoxide hyperglycemic effect of beta-blockers and diazoxide can be enhanced by thiazides. Anticholinergic agents (for example, atropine, biperiden) can increase the bioavailability of thiazide diuretics by weakening the motility of the gastrointestinal tract and slowing down the gastric emptying. Amantadine thiazide diuretics can increase the risk of side effects caused by Amantadin. Cytotoxic drugs (for example, cyclophosphamide, methotrexate) thiazide diuretics can reduce the excretion of cytotoxic drugs with kidneys and enhance their myelosupressive effect. Baclofen, Amifostin based on their pharmacological properties, we can expect that the following drugs can enhance the antihypertensive effect of all antihypertensive drugs, including telmisartan. Alcohol, barbiturates, narcotic drugs, antidepressants can aggravate orthostatic hypotension. Special instructions of the hepatic deficiency of Telzap Plus should not be prescribed to patients with cholestasis, biliary obstruction or severe liver failure (see the “Contraindications” section), since telmisartan is mainly excreted by bile. In these patients, reduced hepatic clearance for telmisartan may be expected. In addition, Telzap Plus should be used with caution in patients with impaired liver function or a progressive liver disease, since minor changes in the balance of fluid and electrolytes can contribute to the liver coma. There is no clinical experience in using telzap plus in patients with impaired liver function. Renovascular hypertension has an increased risk of severe hypotension and renal failure in patients with bilateral stenosis of the renal arteries or arterial stenosis of one functioning kidney that receive drugs affecting the renin-angiotensin-aldosterone system. The renal failure and kidney transplantation of Telzz Plus should not be prescribed to patients with severe renal failure (creatinine clearance <30 ml / min) (see section “Contraindications”). There is no experience of using telzz plus in patients with recent kidney transplantation. The experience of using Telzz Plus is insignificant in patients with mild and moderate renal failure, so periodic monitoring of potassium, creatinine and uric acid in blood serum is recommended. Azotemia associated with the use of thiazide diuretics can occur in patients with impaired renal function. A decrease in the volume of circulating blood (BCC) symptomatic hypotension, especially after the first dose, can occur in patients with reduced BCCs and/or sodium content due to intensive use of diuretics, dietary limitation of salt, diarrhea or vomiting. Such states should be adjusted before the introduction of Telzap Plus. Double blockade of the renin-angiotensinzinzine-aldosterone system as a result of inhibiting the renin-angiotensin-aldosterone system in susceptible persons reported the occurrence of hypotension, fainting, hyperkalemia and changes in the renal function (including acute renal failure), especially when combining drugs that affect This system. The double blockade of the Renin-Angotensin-Aldosterone system (for example, when prescribing telmisartan with other blockers of the Renin-angiotensin-aldosterone system) is not recommended. Careful monitoring of the renal function is recommended if cooled. Other states related to stimulation of the renin-angiotensin-aldosterone system in patients in whom vascular tone and kidney function depend mainly on the activity of the renin-angiotensin-aldosterone system (for example, patients with severe stagnation of heart failure or kidney diseases, including an renal stenosis Arteries), treatment with drugs that affect this system can cause acute hypotension, hyperazotemia, oliguria or in rare cases acute renal failure (see section “side effects”). Primary aldosteronism patients with primary aldosteronism will not respond to antihypertensive drugs acting by inhibiting the Renin-angiotensin system. Thus, the use of Telzap Plus is not recommended. Stenosis of the aortic and mitral valve, obstructive hypertrophic cardiomyopathy like other vasodilating drugs, special caution should be given to patients with aortic or mitral stenosis or obstructive hypertrophic cardiomyopathy. Metabolic and endocrine effects of thiazide therapy can lead to impaired glucose tolerance with hypoglycemia in patients with diabetes with insulin therapy or antiabetic therapy and the treatment of telmisartan. Therefore, these patients should consider monitoring the level of glucose in the blood; If necessary, it may be necessary to adjust the dose of insulin or antidiabetic drugs. Latent diabetes can manifest itself during thiazide therapy. An increase in cholesterol and triglycerides was associated with therapy with thiazide diuretics, however, a dose of 12.5 mg contained in Telzor Plus led to a minimum effect or its absence. Some patients receiving thiazide therapy may occur hyperuricemia or gout develop.
