Telzap Plus, tablets 12.5mg+80 mg 30 pcs

Telzap^® Plus is a combination of telmisartan (angiotensin II receptor antagonist (ARA II)) and hydrochlorothiazide (thiazide diuretic). Combination of these components has a more significant antihypertensive effect, and BP decreases more than with monotherapy with these components.

The drug used once daily in therapeutic doses effectively and gradually reduces BP.

Telmisartan

Telmisartan is a specific angiotensin II receptor antagonist (AT₁ subtype) effective when taken orally. Telmisartan has a high affinity for the AT₁ subtype of angiotensin II receptors, through which angiotensin II action is realized. Telmisartan displaces angiotensin II from binding to the receptor without exhibiting AT₁ receptor agonist properties. Telmisartan selectively and persistently binds to the AT₁ receptor. Telmisartan has no affinity for other receptors, including AT₂ and other less understood AT receptors. The functional role of these receptors, as well as the effect of their possible increased stimulation by angiotensin II, the concentration of which is increased by telmisartan, has not been studied. Telmisartan reduces plasma aldosterone concentration, does not inhibit renin and does not block ion channels. Telmisartan does not inhibit ACE (kininase II), which also destroys bradykinin. This avoids the side effects associated with the action of bradykinin.

In healthy subjects, telmisartan at a dose of 80 mg almost completely blocks the hypertensive effects of angiotensin II. The suppressive effect lasts for more than 24 h and lasts up to 48 h.

The onset of antihypertensive action is observed within the first 3 h after oral administration of telmisartan. Duration of the therapeutic effect of the drug is more than 24 h and includes the last 4 h before taking the next dose according to daily blood pressure monitoring. This is confirmed by measurements taken at the time of maximum effect and immediately before the next dose (the ratio of residual effect to maximum effect is higher than 80% for doses of 40 and 80 mg telmisartan in placebo-controlled trials). Maximum antihypertensive effect develops after 4-8 weeks of regular telmisartan use and persists during long-term therapy.

In patients with arterial hypertension telmisartan reduces both systolic and diastolic blood pressure without affecting HR. According to the results of clinical studies, the effectiveness of telmisartan antihypertensive effect is comparable to the therapeutic effect of drugs of other classes, such as amlodipine, atenolol, enalapril, hydrochlorothiazide and lisinopril. In case of abrupt discontinuation of telmisartan treatment BP gradually returns to baseline values, without development of “withdrawal” syndrome.

The incidence of dry cough was significantly lower with telmisartan compared to ACE inhibitors.

Hydrochlorothiazide

Hydrochlorothiazide is a thiazide diuretic. Thiazides affect reabsorption of electrolytes in the renal tubules, thereby increasing the excretion of sodium and chloride ions in approximately equivalent amounts. Diuretic effect of hydrochlorothiazide leads to decreased RBC, increased plasma renin activity, increased production of aldosterone with subsequent increase of urinary potassium and bicarbonate content and decreased plasma potassium content. Concomitant use of telmisartan contributes to the reduction of potassium loss caused by this diuretic, probably due to the blockade of the RAAS. After hydrochlorothiazide administration, diuresis increases in 2 hours, the maximum effect develops in about 4 hours, the effect lasts about 6-12 hours.

In epidemiological studies it has been found that long-term therapy with hydrochlorothiazide reduces the risk of cardiovascular morbidity and mortality.

Patients in children and adolescents

The safety and efficacy of telmisartan in children and adolescents younger than 18 years has not been established.

Indications

Active ingredient

How to take, the dosage

The drug is taken orally once daily with fluids, regardless of meals.

Patients whose BP cannot be adequately controlled with telmisartan or hydrochlorothiazide monotherapy should take Telzap® Plus. Individual dose titration of each component is recommended before switching to a fixed-dose combination. In some clinical situations, a direct switch from monotherapy to fixed-dose combination treatment may be considered.

Telzap® Plus, 80 mg+12.5 mg, may be used once daily in patients whose BP cannot be adequately controlled with an 80 mg/day dose of telmisartan.

Dose adjustment is not required in patients with mild to moderate renal dysfunction (CKG greater than 30 ml/min). Periodic monitoring of renal function parameters is recommended.

The concomitant use of telmisartan with aliskiren is contraindicated in patients with renal impairment (FFR less than 60 mL/min/1.73 m2).

The drug Telzap® Plus is contraindicated in patients with liver dysfunction.

Dose adjustment is not required for elderly patients (over 70 years of age).

The drug Telzap® Plus is contraindicated in children and adolescents under the age of 18 years due to lack of safety and efficacy data.

Interaction

Double RAAS blockade

The concomitant use of telmisartan with drugs containing aliskiren is contraindicated in patients with diabetes mellitus or renal impairment (FFR < 60 ml/min/1.73 m2) and is not recommended in other patients.

The concomitant use of ACE inhibitors with ARA II or drugs containing aliskiren is associated with an increased risk of arterial hypotension, hyperkalemia and decreased renal function (including acute renal failure) in patients compared to use of each drug alone.

The use of a combination of ACE inhibitors and ARA II is contraindicated in patients with diabetic nephropathy.

Digoxin

Concomitant use of telmisartan with digoxin showed an average increase in peak plasma concentration (49%) and minimum concentration (20%) of digoxin. When concomitant administration, blood digoxin concentrations should be monitored at initiation of treatment, dose adjustment and discontinuation of telmisartan treatment to maintain them within the therapeutic range.

Drugs causing potassium loss and hypokalemia

Other potassium diuretics, laxatives, corticosteroids, ACTH, amphotericin, carbenoxolone, penicillin G sodium salt, salicylic acid and its derivatives. If concomitant use of these drugs with telmisartan/hydrochlorothiazide combination is necessary, it is recommended to monitor the plasma potassium content. These drugs may increase potassium loss when used concomitantly with hydrochlorothiazide.

Drugs causing increased plasma potassium

As with other drugs acting on the RAAS, the use of telmisartan/hydrochlorothiazide combination may cause hyperkalemia. The risk may increase when concomitant use with other drugs that can cause hyperkalemia (table salt substitutes containing potassium, potassium-saving diuretics, ACE inhibitors, ARA II, NSAIDs, including selective COX-2 inhibitors, heparin, immunosuppressants (cyclosporine or tacrolimus) and trimethoprim).

Combination with ACE inhibitors or NSAIDs is less risky if strict precautions are taken.

When these drugs must be used concomitantly with the telmisartan/hydrochlorothiazide combination, monitoring of plasma potassium is recommended.

Lithium

Concomitant use of lithium drugs with ACE inhibitors and rarely with ARA II, including the combination telmisartan/hydrochlorothiazide, reversible increase in plasma lithium concentration and its toxic effects have been observed. When using them concomitantly with lithium preparations, careful monitoring of plasma lithium concentrations is recommended.

NSAIDs

. NSAIDs (including acetylsalicylic acid in doses used for anti-inflammatory treatment (not more than 3 g/day), COX-2 inhibitors and non-selective NSAIDs) can weaken the antihypertensive effect of APA II and can impair the diuretic, natriuretic effect of thiazide diuretics.

In some patients with impaired renal function (e.g., dehydrated patients with decreased RBC, elderly patients) concomitant use of APA II and COX-inhibiting drugs may lead to further deterioration of renal function up to and including development of acute renal failure, which is usually reversible. Therefore, concomitant use of telmisartan/hydrochlorothiazide combination with NSAIDs should be used with caution, especially in elderly patients. Patients should be provided with adequate fluid intake, in addition, at the beginning of concomitant use and periodically thereafter, renal function should be monitored.

There have been no clinically significant interactions with ibuprofen or paracetamol when telmisartan is concomitantly administered.

Drugs susceptible to changes in plasma potassium

We recommend periodic monitoring of plasma potassium and ECG during use with drugs that are susceptible to changes in plasma potassium (e.g., cardiac glycosides, antiarrhythmic drugs) and after an attack of ventricular tachycardia, including those caused by drugs (e.g., cardiac tachycardia).including those caused by drugs (including some antiarrhythmic drugs). Hypokalemia has been a provoking factor for the development of torsade de pointes ventricular tachycardia:

– Class IA antiarrhythmic drugs (e.g., quinidine, hydroquinidine, disopyramide);

– Class III antiarrhythmic drugs (e.g., amiodarone, sotalol, dofetilide, ibutilide);

– Certain neuroleptics (e.g., thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, sultopride, amisulpride, thiapride, pimozide, haloperidol, droperidol);

Other drugs (e.g., bepridil, cisapride, difemenil, erythromycin [IV injection], halofantrine, misolastin, pentamidine, sparfloxacin, terfenadine, vincamine [IV injection]).

Cardiac glycosides

Hypokalemia or hypomagnesemia caused by hydrochlorothiazide administration may contribute to arrhythmias with cardiac glycoside therapy.

Other hypotensive drugs

Telmisartan may increase the effect of other hypotensive drugs.

Antidiabetic drugs (oral medications and insulin)

Doses of antidiabetic drugs may need to be adjusted.

Metformin

Metformin should be used with caution because of the risk of lactacidosis caused by possible functional renal failure with hydrochlorothiazide.

Cholestyramine and colestipol

The absorption of hydrochlorothiazide is reduced in the presence of anion exchange resins.

Presor amines (e.g., norepinephrine (noradrenaline)

The action of vasopressor amines may be impaired.

Nondepolarizing skeletal muscle myorelaxants (e.g., tubocurarin)

The action of nondepolarizing myorelaxants may be enhanced by hydrochlorothiazide.

Antipodagric agents (e.g., probenecid, sulfinpyrazone, and allopurinol)

It may be necessary to adjust the dose of drugs that promote uric acid excretion because hydrochlorothiazide may increase plasma levels of uric acid. It may be necessary to increase the dose of probenecid or sulfinpyrazone. Concomitant use of thiazide diuretic may increase the incidence of hypersensitivity reactions to allopurinol.

Calcium salts

Hydrochlorothiazide may increase plasma calcium levels due to reduced calcium excretion. If calcium supplementation is necessary, plasma calcium concentrations should be monitored and the dose should be adjusted accordingly.

Thiazides may interfere with the results of tests to evaluate parathyroid function due to their effect on calcium metabolism.

β-adrenoreceptor blockers and diazoxide

The hyperglycemic effects of β-adrenoreceptor blockers and diazoxide may be enhanced by hydrochlorothiazide.

Cholinolytic agents (e.g., atropine, biperiden)

Cholinolytic agents may increase the bioavailability of hydrochlorothiazide by reducing GI motility and gastric emptying rate.

Amantadine

Hydrochlorothiazide may increase the risk of amantadine-induced adverse reactions.

Glycyrrhizic acid

The interaction of hydrochlorothiazide and licorice root (glycyrrrhizic acid) may lead to hypokalemia.

Cytotoxic drugs (e.g., cyclophosphamide, methotrexate)

Hydrochlorothiazide may decrease renal excretion of cytotoxic drugs and increase their myelosuppressive effects.

Based on the pharmacological properties of baclofen and amifostine, it can be assumed that they will enhance the therapeutic effect of all hypotensive agents, including telmisartan.

In addition, orthostatic hypotension may be increased with alcohol, barbiturates, narcotics or antidepressants.

Corticosteroids (for systemic use)

Corticosteroids impair the antihypertensive effect of telmisartan.

Special Instructions

Hepatic impairment

The use of Telzap>® Plus is contraindicated in patients with cholestasis, biliary obstruction and/or impaired liver function because telmisartan is mainly excreted with bile. There is reason to believe that hepatic clearance of telmisartan is reduced in these patients.

Renovascular hypertension

Patients with bilateral renal artery stenosis or artery stenosis of a single functioning kidney have an increased risk of significant BP reduction and acute renal failure when treated with drugs acting on the RAAS.

Double RAAS blockade

The data on concomitant use of ACE inhibitors with ARA II or with drugs containing aliskiren confirm the increased risk of a sharp decrease in BP, development of hyperkalemia and decreased renal function (including acute renal failure). Therefore, the use of this drug combination is contraindicated. If dual RAAS blockade is necessary each case should be considered individually and renal function, electrolyte-water balance and BP should be monitored carefully.

A combination of ACE inhibitors and ARA II is contraindicated in patients with diabetic nephropathy.

Other conditions associated with RAAS stimulation

In patients whose vascular tone and renal function are predominantly dependent on RAAS activity (e.g., patients with significant chronic heart failure or existing renal disease, including renal stenosis).In patients with severe chronic heart failure or existing renal disease, including renal artery stenosis), the use of medications acting on this system, such as telmisartan, is associated with the occurrence of acute BP decrease, hyperazotemia, oliguria, or rarely with the development of acute renal failure.

Primary hyperaldosteronism

In patients with primary hyperaldosteronism, treatment with antihypertensive drugs that work by inhibiting the RAAS is generally ineffective. Therefore, the use of Telzap® Plus is not recommended.

Renal dysfunction and renal transplantation

The use of Telzap®Plus is contraindicated in patients with severe renal dysfunction (CK < 30 ml/min). There is no experience of using the drug in patients who underwent kidney transplantation shortly before use. Since the experience of Telzap®® Plus administration in patients with mild to moderate renal dysfunction is limited, it is recommended to perform periodic monitoring of plasma potassium, creatinine and uric acid as well as renal function parameters. In patients with impaired renal function there may be azotemia associated with the use of thiazide diuretics.

Decreased BP, especially after the first administration of Telzap® Plus, may occur in patients with decreased RBC and/or low plasma sodium levels with prior treatment with diuretics, restriction of table salt intake, diarrhea or vomiting. Such conditions (fluid and/or sodium deficiency) should be eliminated before starting Telzap® Plus.

Aortic or mitral valve stenosis, obstructive hypertrophic cardiomyopathy

As with other vasodilators, patients with aortic or mitral stenosis and hypertrophic obstructive cardiomyopathy require special caution.

Effects on metabolism and endocrine function

The use of hydrochlorothiazide may impair glucose tolerance, and patients with diabetes may develop hypoglycemia with concurrent use of insulin or hypoglycemic agents and telmisartan. Dose adjustment of hypoglycemic agents, including insulin, may be required. During thiazide treatment, patients with impaired glucose tolerance may manifest latent diabetes mellitus. Treatment with thiazide diuretics is associated with increased concentration of cholesterol and triglycerides in blood plasma. However, when using the drug containing 12.5 mg of hydrochlorothiazide, this effect is minimal or absent. In some patients using hydrochlorothiazide, hyperuricemia or sudden exacerbation of gout may occur.

Disruption of water-electrolyte balance

Per use of Telzap® Plus requires periodic monitoring of plasma electrolytes.

The thiazides including hydrochlorothiazide may cause electrolyte-water balance disorders (hypokalemia, hyponatremia and hypochloremic alkalosis) and acid-base balance changes. Signs of electrolyte-water balance disorders are: dry mouth, thirst, general weakness, lethargy, sleepiness, restlessness, pain or muscle cramps, muscle weakness, decreased blood pressure, oliguria, tachycardia and GI disorders such as nausea and vomiting.

Hypokalemia

While hypokalemia may occur due to hydrochlorothiazide, concomitant therapy with telmisartan may compensate for decreased plasma potassium concentrations. The risk of hypokalemia increases in patients with cirrhosis, patients with significant diuresis, patients on a salt-free diet, patients who do not adequately replenish electrolyte loss, and patients receiving concomitant therapy with corticosteroids or ACTH.

Hyperkalemia

The administration of telmisartan may cause hyperkalemia. However, clinically significant hyperkalemia during Telzap® Plus administration has not been observed. The main risk factors for the development of hyperkalemia are:

– diabetes mellitus, renal insufficiency, heart failure, elderly age (patients over 70 years);

– combination with one or more drugs acting on the RAAS and/or supplements containing potassium. Drugs that can cause hyperkalemia are potassium-saving diuretics, ACE inhibitors, ARA II, NSAIDs, including selective COX-2 inhibitors, heparin, immunosuppressants (cyclosporine or tacrolimus), trimethoprim, and table salt substitutes containing potassium. – Concomitant conditions, particularly dehydration, acute heart failure, metabolic acidosis, acute renal failure (e.g., in infectious diseases), cytolysis syndrome (e.g., acute limb ischemia, rhabdomyolysis, extensive trauma).

Patients at risk are advised to carefully monitor plasma potassium levels.

Hyponatremia and hypochloremic alkalosis

There is no evidence that Telzap® Plus reduces or prevents diuretic-induced hyponatremia. Minor chlorine deficiency usually does not require correction.

Hypercalcemia

Hydrochlorothiazide may decrease urinary calcium excretion and cause intermittent and mild increases in plasma calcium in the absence of any calcium metabolism disorder. Severe hypercalcemia may be a sign of occult hyperparathyroidism. Administration of hydrochlorothiazide should be discontinued before parathyroid function test.

Hypomagnesemia

An increased urinary magnesium excretion has been noted with hydrochlorothiazide, which may lead to hypomagnesemia.

Sorbitol

This drug contains sorbitol (E420). In patients with rare hereditary fructose intolerance the use of Telzap® Plus is contraindicated.

Ethnic differences

Like all other ARAs II, telmisartan is less effective in reducing BP in patients of the Negro race than in other races, possibly due to a greater predisposition to decreased renin activity in these patient populations. During post-registration use, most cases of functional impairment of hepatic function or liver damage occurred in Japanese patients. The Japanese are more prone to develop these adverse reactions.

IBS and cerebrovascular disease

As with any other hypotensive medication, excessive BP reduction in patients with IBS or cerebrovascular disease may lead to myocardial infarction or stroke.

Heart failure

As with other drugs acting on the RAAS, patients with heart failure (with or without impaired renal function) are at risk of developing a significant decrease in BP as well as impaired renal function (often acute).

Hypersensitivity reactions to hydrochlorothiazide are most likely to occur in patients who have a history of allergic reactions or bronchial asthma. It is known that the use of thiazide diuretics, including hydrochlorothiazide, may lead to exacerbation or exacerbation of symptoms of systemic lupus erythematosus. Photosensitivity reactions have been reported with hydrochlorothiazide. In case of photosensitivity reactions, it is recommended to discontinue Telzap® Plus. If the use of diuretics is still necessary, it is recommended to protect exposed skin from sunlight or artificial ultraviolet irradiation.

Acute myopia and closed-angle glaucoma

The administration of hydrochlorothiazide may cause an idiosyncratic reaction leading to acute transient myopia and acute closed-angle glaucoma. Symptoms of these disorders are a sudden decrease in visual acuity or eye pain and usually occur within hours to weeks after the start of treatment. Acute closed angle glaucoma that is not promptly treated can lead to permanent vision loss. First of all, Telzap® Plus should be discontinued immediately. Emergency conservative or surgical treatment may be necessary if intraocular pressure is not controlled. A history of allergic reaction to sulfonamides or penicillin are risk factors for acute closed-angle glaucoma.

Interstitial lung disease

In clinical use, cases of interstitial lung disease have been described with telmisartan.

Impact on driving and operating machinery

When driving motor vehicles and engaging in potentially hazardous activities, it should be noted that dizziness and somnolence may occur while taking Telzap® Plus, which requires caution.

Contraindications

– cholestasis and obstructive biliary tract disease;

– hepatic dysfunction;

– severe renal dysfunction (CKD less than 30 ml/min);

– concomitant use with drugs containing aliskiren in patients with diabetes mellitus or renal impairment (FFR less than 60 mL/min/1.73 m2);

– concomitant use with ACE inhibitors in patients with diabetic nephropathy;

p> – refractory hypokalemia, hypercalcemia;

– hereditary fructose intolerance (contains sorbitol).

– pregnancy;

– period of breastfeeding;

– age under 18 years (effectiveness and safety are not established);

– hypersensitivity to the active substance or any excipients of the drug and to other sulfonamide derivatives.

With caution, the drug should be prescribed in bilateral renal artery stenosis or stenosis of the artery of the sole kidney, severe renal function impairment; reduction of the BOD on previous therapy with diuretics, restriction of table salt intake, diarrhea or vomiting; hyperkalemia; conditions after kidney transplantation (no experience of use); chronic heart failure III-IV classifications NYHA; stenosis of aortic and mitral valves; Idiopathic hypertrophic subaortic stenosis; hypertrophic obstructive cardiomyopathy; CHD and cerebrovascular disease; diabetes; primary hyperaldosteronism; gout; Water-electrolyte balance disorders (including hypokalemia, hyponatremia, hypochloremic alkalosis, hypomagnesemia); hyperuricemia; closed angle glaucoma (due to the presence of hydrochlorothiazide); systemic lupus erythematosus; patients of non-high blood type; elderly patients (>70 years).

The experience of use in patients with renal insufficiency (CKR greater than 30 ml/min) is limited, but there is no evidence of renal side effects, and no dose adjustment is required.

Side effects

The most frequently reported adverse reaction was dizziness. Serious angioedema was rare (≥1/10,000, < 1/1000).

Telzap Plus 80 mg+12.5 mg: the overall incidence of adverse reactions was comparable to that of telmisartan monotherapy. No dose-dependence of the development of adverse reactions has been established, and no correlation with gender, age or race of patients has been noted.

The adverse reactions are divided into systemic organ classes according to MedDRA. The frequency of adverse effects was determined according to the WHO classification: very common (≥1/10), common (≥1/100, < 1/10), infrequent (≥1/1000, < 1/100), rare (≥1/10 000, < 1/1000), very rare (< 1/10 000), including individual reports; frequency unknown (the frequency of adverse effects could not be determined from available data).

Infectious and parasitic diseases: rarely – bronchitis, pharyngitis, sinusitis.

Immune system disorders: rare – increase of symptoms or exacerbation of systemic lupus erythematosus (during post-registration monitoring).

Metabolism and nutrition: infrequent hypokalemia; rarely – hyperuricemia, hyponatremia.

Mental disorders: infrequent – anxiety; rarely – depression.

Nervous system disorders: frequently – dizziness; infrequently – syncope, paresthesia; rarely – insomnia, sleep disturbance.

An organ of vision: rare – visual impairment, transient visual clarity.

Hearing organ: infrequent – vertigo.

Cardiovascular system: infrequent – tachycardia, arrhythmia, arterial hypotension, orthostatic hypotension.

Respiratory system: infrequent dyspnea; rarely – respiratory distress syndrome (including pneumonitis and pulmonary edema).

The digestive system: infrequent – diarrhea, dry mouth, flatulence; rarely – abdominal pain, constipation, dyspepsia, vomiting, gastritis.

Liver and biliary tract: rarely – liver dysfunction and liver disease.

Skin and subcutaneous tissue disorders: rarely – angioedema (also fatal), erythema, skin itching, skin rash, increased sweating, urticaria.

Muscular system and connective tissue disorders: infrequent back pain, muscle cramps, myalgia; rarely – joint pain, muscle cramps, pain in extremities.

Gender and mammary gland disorders: infrequent – erectile dysfunction.

General disorders and disorders at the site of administration: infrequent – pain in the chest; rarely – flu-like syndrome, pain.

Laboratory and instrumental studies: rarely – increased plasma creatinine concentration, increased CPK activity, increased liver transaminase activity.

Additional information about individual components

Some side effects noted with the use of one of the components, the development of which may be expected with the combination of telmisartan and hydrochlorothiazide.

Telmisartan

The incidence of adverse reactions with telmisartan reported in controlled clinical trials was comparable to the incidence of adverse reactions noted in the placebo group (41.4% and 43.9%, respectively). The following adverse reactions have been reported in a clinical trial of telmisartan, including a group of high cardiovascular risk patients over the age of 50 years.

Infectious and parasitic diseases: infrequent – upper respiratory tract infections, urinary tract infections, including cystitis; rarely – sepsis, including fatal.

Hematopoietic system: infrequent anemia; rarely – eosinophilia, thrombocytopenia.

The immune system: rare – hypersensitivity reactions, anaphylactic reactions.

Metabolism and nutrition: infrequent hyperkalemia; rarely – hypoglycemia (in patients with diabetes).

Nervous system disorders: rarely – somnolence.

Cardiovascular system disorders: infrequent – bradycardia.

Respiratory system: infrequent – cough; very rare – interstitial lung disease.

Digestive system disorders: rare – feeling of discomfort in the stomach area.

Skin and subcutaneous tissue: rarely – eczema, drug rash, toxic skin rash.

Muscular system disorders: rare – arthrosis, pain in the tendon area.

Urinary system disorders: infrequent – renal dysfunction (including acute renal failure).

General disorders and disorders at the site of administration: infrequent – asthenia.

Laboratory and instrumental studies: rarely – decrease in hemoglobin.

Hydrochlorothiazide

Hydrochlorothiazide may cause or increase hypovolemia, which may lead to impaired water-electrolyte balance. The adverse reactions reported with hydrochlorothiazide are listed below.

Infectious and parasitic diseases: frequency is unknown – sialoadenitis.

Hematopoietic system: frequency unknown – aplastic anemia, hemolytic anemia, suppression of bone marrow function, leukopenia, neutropenia, agranulocytosis, thrombocytopenia.

Immune system disorders: frequency unknown – anaphylactic reactions, hypersensitivity reactions.

Endocrine system disorders: frequency unknown – lack of proper glycemic control in diabetes mellitus.

Metabolism and nutrition: frequency unknown – anorexia, loss of appetite, disruption of water-electrolyte balance, hypovolemia.

Mental disorders: frequency is unknown – agitation.

Nervous system disorders: frequency unknown – preconsciousness.

An organ of vision: frequency unknown – xanthopsia, acute myopia, acute closed-angle glaucoma.

Vascular disorders: frequency unknown – necrotizing vasculitis.

Gastrointestinal system: frequency unknown – pancreatitis, feeling of discomfort in the stomach area.

Liver and biliary tract: frequency unknown – jaundice (parenchymatous or cholestatic).

Skin and subcutaneous tissue disorders: frequency unknown – lupus-like syndrome, photosensitivity reactions, skin vasculitis, toxic epidermal necrolysis (Lyell’s syndrome).

Urinary system disorders: frequency unknown – interstitial nephritis, impaired renal function, glucosuria.

Skeletal system and connective tissue: frequency unknown – weakness.

General disorders and disorders at the site of administration: frequency unknown – hyperthermia.

Laboratory and instrumental findings: frequency unknown – hypertriglyceridemia, hypercholesterolemia, hyperglycemia.

Overdose

No cases of overdose have been identified. Possible symptoms are composed of the symptoms of overdose of individual components.

Symptoms

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

With overdose of hydrochlorothiazide reduction of electrolytes (hypokalemia, hypochloremia) and hypovolemia with excessive diuresis are associated. The most common symptoms of overdose are nausea and somnolence. Hypokalemia may lead to muscle spasm and/or exacerbation of arrhythmia when used simultaneously with cardiac glycosides or certain antiarrhythmic agents.

Treatment

Telmisartan is not excreted by hemodialysis. The degree of excretion of hydrochlorothiazide by hemodialysis has not been determined. Patients should be closely monitored and symptomatic as well as supportive treatment should be provided. The approach to treatment depends on the time elapsed after taking the drug and the severity of symptoms. Recommended measures include inducing vomiting and/or gastric lavage, and administration of activated charcoal is advisable. The patient should be placed on his back with his legs elevated. If necessary, it is advisable to replenish the blood circulation, e.g., by intravenous injection of 0.9% sodium chloride solution. Sympathomimetic drugs may be prescribed.

Pregnancy use

Pregnancy

The treatment of ARA II during pregnancy is contraindicated. The use of ARA II is not recommended in the first trimester of pregnancy and is contraindicated in the second and third trimesters of pregnancy.

Telmisartan

There are no adequate data on the use of telmisartan in pregnant women. Animal studies have found its reproductive toxicity. Epidemiologic evidence for the risk of teratogenic effects after ACE inhibitors in the first trimester of pregnancy has not been conclusive, however, this risk cannot be excluded. Until controlled epidemiological studies are available regarding the risk of ARA II administration, a similar risk may exist for this class of drugs. Except as a last resort, patients planning to become pregnant should choose an alternative antihypertensive medication with a proven safety profile in pregnancy. Once pregnancy has been established, APA II treatment should be discontinued immediately and alternative treatment should be initiated if necessary.

The treatment with ARA II in the second and third trimesters of pregnancy has toxic effects on the fetus (impaired renal function, oligohydramnios, delayed cranial ossification) and the newborn (renal failure, arterial hypotension and hyperkalemia). An ultrasound examination of the fetal kidneys and skull is recommended during the use of ARA II from the second trimester of pregnancy. Children whose mothers have taken APA II should be carefully examined for arterial hypotension.

Hydrochlorothiazide

There is limited experience with hydrochlorothiazide during pregnancy, especially in the first trimester. Hydrochlorothiazide penetrates the BBB. Based on the pharmacological mechanism of action of hydrochlorothiazide, its use in the second and third trimesters may impair the fetoplacental blood flow and cause fetal/newborn jaundice, electrolyte-water imbalance and thrombocytopenia. Hydrochlorothiazide should not be used in the treatment of preeclampsia, pregnancy edema, arterial hypertension or preeclampsia because of the risk of decreased RBC and impaired placental blood flow without adequate therapeutic effect on the course of the disease.

Hydrochlorothiazide should not be used to treat essential hypertension in pregnant women except in rare cases where no other treatment is possible.

Breastfeeding

The administration of Telzap® Plus during breastfeeding is contraindicated, alternative treatment with more favorable safety profiles should be used.

Fertility

The effect of the combination of telmisartan and hydrochlorothiazide on human fertility has not been studied.

Similarities