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

– arterial hypertension (in the absence of effectiveness of monotherapy with telmisartan or hydrochlorothiazide).

Pharmacological effect

Telzap Plus is a combination of telmisartan (an angiotensin II receptor antagonist (ARA II)) and hydrochlorothiazide (a thiazide diuretic). The combination of these components provides a more pronounced antihypertensive effect, while the blood pressure level decreases more than with monotherapy with these components.

The drug, used once a day in therapeutic doses, effectively and gradually reduces blood pressure.

Telmisartan

Telmisartan is a specific angiotensin II receptor antagonist (AT1 subtype), effective when taken orally. Telmisartan has a high affinity for the AT1 receptor subtype of angiotensin II, through which the action of angiotensin II is realized. Telmisartan displaces angiotensin II from its connection with the receptor without exhibiting the properties of an AT1 receptor agonist. Telmisartan selectively and persistently binds to the AT1 receptor. Telmisartan has no affinity for other receptors, including AT2 and other less studied 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 increases under the influence of telmisartan, have not been studied. Telmisartan reduces the concentration of aldosterone in the blood plasma, does not inhibit renin and does not block ion channels. Telmisartan does not inhibit ACE (kininase II), which also destroys bradykinin. This avoids side effects associated with bradykinin.

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

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

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

The incidence of dry cough was significantly lower with the use of telmisartan as opposed to ACE inhibitors.

Hydrochlorothiazide

Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the reabsorption of electrolytes in the renal tubules, thereby increasing the excretion of sodium and chloride ions in approximately equivalent quantities. The diuretic effect of hydrochlorothiazide leads to a decrease in blood volume, an increase in plasma renin activity, increased aldosterone production with a subsequent increase in the content of potassium and bicarbonates in the urine and a decrease in the potassium content in the blood plasma. Concomitant use of telmisartan helps reduce potassium loss caused by this diuretic, probably due to blockade of the RAAS. After taking hydrochlorothiazide, diuresis increases after 2 hours, the maximum effect develops after approximately 4 hours, the effect lasts about 6-12 hours.

Epidemiological studies have found that long-term therapy with hydrochlorothiazide reduces the risk of cardiovascular morbidity and mortality.

Patients of childhood and adolescence

The safety and effectiveness of telmisartan in children and adolescents under 18 years of age have not been established.

Special instructions

Liver dysfunction

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

Renovascular hypertension

When treated with drugs acting on the RAAS, in patients with bilateral renal artery stenosis or stenosis of the artery of a single functioning kidney, the risk of a significant decrease in blood pressure and the development of acute renal failure increases.

Double blockade of the RAAS

Data on the simultaneous use of ACE inhibitors with ARB II or with drugs containing aliskiren confirm an increased risk of a sharp decrease in blood pressure, the development of hyperkalemia and decreased renal function (including acute renal failure). Therefore, the use of this drug combination is contraindicated. If it is necessary to carry out double blockade of the RAAS, each case should be considered individually and carefully monitor renal function, water and electrolyte balance and blood pressure levels.

In patients with diabetic nephropathy, the use of a combination of ACE inhibitors and ARB II is contraindicated.

Other conditions associated with stimulation of the RAAS

In patients whose vascular tone and renal function depend primarily on the activity of the RAAS (for example, patients with severe chronic heart failure or existing kidney disease, including renal artery stenosis), the use of drugs acting on this system, such as telmisartan, is associated with the occurrence of an acute decrease in blood pressure, hyperazotemia, oliguria, or rarely with the development of 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®Plus is not recommended.

Renal dysfunction and kidney transplantation

The use of Telzap® Plus is contraindicated in patients with severe renal impairment (creatinine clearance <30 ml/min). There is no experience with the use of the drug in patients who shortly before use underwent a kidney transplant. Since experience with the use of Telzap® Plus in patients with mild to moderate renal impairment is limited, it is recommended to periodically monitor the content of potassium, creatinine and uric acid in the blood plasma, as well as indicators of renal function. In patients with impaired renal function, azotemia may occur due to the use of thiazide diuretics.

Decrease in BCC

A decrease in blood pressure, especially after the first dose of Telzap® Plus, may occur in patients with reduced blood volume and/or low 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) must be eliminated before taking Telzap® Plus.

Aortic or mitral valve stenosis, obstructive hypertrophic cardiomyopathy

As with other vasodilators, patients with aortic or mitral stenosis, as well as hypertrophic obstructive cardiomyopathy, should be especially careful.

Effect on metabolism and endocrine function

The use of hydrochlorothiazide may impair glucose tolerance, and in patients with diabetes mellitus hypoglycemia may develop during the simultaneous use of insulin or hypoglycemic agents and telmisartan. Dosage adjustment of hypoglycemic agents may be required, incl. insulin. During treatment with thiazides in patients with impaired glucose tolerance, the manifestation of latent diabetes mellitus is possible. Treatment with thiazide diuretics is associated with an increase in the concentration of cholesterol and triglycerides in the blood plasma. However, when using a drug containing 12.5 mg of hydrochlorothiazide, this effect is minimal or absent. Some patients using hydrochlorothiazide may develop hyperuricemia or a sudden onset of gout flare-up.

Water-electrolyte imbalance

When using the drug Telzap® Plus, it is necessary to periodically monitor the content of electrolytes in the blood plasma.

Thiazides, including hydrochlorothiazide, can cause fluid and electrolyte imbalances (hypokalemia, hyponatremia and hypochloremic alkalosis) and changes in acid-base status. Signs of water and electrolyte imbalance are: dry mouth, thirst, general weakness, lethargy, drowsiness, anxiety, muscle pain or cramps, muscle weakness, decreased blood pressure, oliguria, tachycardia and gastrointestinal disorders such as nausea and vomiting.

Hypokalemia

Although hypokalemia may occur due to the use of hydrochlorothiazide, concomitant therapy with telmisartan may compensate for the decrease in plasma potassium concentration. The risk of hypokalemia increases in patients with cirrhosis, patients with severe diuresis, those on a salt-free diet, patients who do not adequately replace lost electrolytes, and also in patients receiving concomitant therapy with corticosteroids or ACTH.

Hyperkalemia

Taking telmisartan may cause the development of hyperkalemia. However, no clinically significant hyperkalemia was observed while taking Telzap® Plus. The main risk factors for the development of hyperkalemia are:

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

– combination with one or more drugs acting on the RAAS and/or supplements containing potassium. Medicines that can cause hyperkalemia are potassium-sparing diuretics, ACE inhibitors, ARB II, NSAIDs, incl. selective COX-2 inhibitors, heparin, immunosuppressants (cyclosporine or tacrolimus), trimethoprim, and salt substitutes containing potassium;

– concomitant diseases, especially dehydration, acute heart failure, metabolic acidosis, acute renal failure (for example, in infectious diseases), cytolysis syndrome (for example, acute limb ischemia, rhabdomyolysis, major 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 the development of diuretic-induced hyponatremia. Minor chlorine deficiency usually does not require correction.

Hypercalcemia

Hydrochlorothiazide may reduce urinary calcium excretion and cause periodic and slight increases in plasma calcium in the absence of any disturbances in calcium metabolism. Severe hypercalcemia may be a sign of hidden hyperparathyroidism. Hydrochlorothiazide should be discontinued before parathyroid function tests are performed.

Hypomagnesemia

While taking hydrochlorothiazide, an increase in the excretion of magnesium in the urine was noted, which can lead to hypomagnesemia.

Sorbitol

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

Ethnic differences

Like all other II receptor antagonists, telmisartan is 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. During post-marketing use, the majority of cases of hepatic dysfunction or liver injury occurred in Japanese subjects. The Japanese are more predisposed to developing these adverse reactions.

IHD and cerebrovascular disease

As with any other antihypertensive drugs, an excessive decrease in blood pressure in patients with coronary artery disease or cerebrovascular disease can lead to the development of myocardial infarction or stroke.

Heart failure

As with other drugs that affect the RAAS, patients with heart failure (with or without renal impairment) are at risk of developing a significant decrease in blood pressure, as well as renal dysfunction (often acute).

General violations

Hypersensitivity reactions to hydrochlorothiazide are most likely to occur in patients with a history of allergic reactions or asthma. It is known that the use of thiazide diuretics, including hydrochlorothiazide, can lead to exacerbation or worsening of symptoms of systemic lupus erythematosus. Photosensitivity reactions have been observed with the use of hydrochlorothiazide. If a photosensitivity reaction occurs, it is recommended to stop taking Telzap® Plus. If the use of diuretics is still necessary, it is recommended to protect exposed skin from exposure to sunlight or artificial ultraviolet irradiation.

Acute myopia and angle-closure glaucoma

Hydrochlorothiazide may cause an idiosyncratic reaction leading to acute transient myopia and acute angle-closure glaucoma. Symptoms of these disorders include a sudden decrease in visual acuity or eye pain and usually occur between a few hours and a few weeks after starting treatment. If acute angle-closure glaucoma is not treated in a timely manner, it can lead to permanent vision loss. First of all, you should immediately stop taking Telzap® Plus. If intraocular pressure is not controlled, emergency conservative or surgical treatment may be required. Risk factors for the development of acute angle-closure glaucoma include a history of an allergic reaction to sulfonamides or penicillin.

Interstitial lung diseases

During clinical use, cases of interstitial lung diseases while taking telmisartan have been described.

Impact on the ability to drive vehicles and operate machinery

When driving vehicles and engaging in potentially hazardous activities, it should be taken into account that dizziness and drowsiness may occur while taking Telzap® Plus, which requires caution.

Active ingredient

Hydrochlorothiazide, Telmisartan

Composition

1 tab.:

Pregnancy

Pregnancy

Treatment with 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 it to be reproductively toxic. Epidemiological evidence of the risk of teratogenicity after taking ACE inhibitors in the first trimester of pregnancy was not convincing, however, this risk cannot be excluded. While there is no data from controlled epidemiological studies regarding the risk of taking ARB II, a similar risk may exist for this class of drugs. Unless there is an urgent need for long-term treatment with ARB II, patients planning pregnancy should choose an alternative antihypertensive drug with a proven safety profile for use in pregnancy. Once pregnancy is established, treatment with ARA II should be stopped immediately and, if necessary, alternative treatment should be started.

Treatment of ARA II 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 ARA II from the second trimester of pregnancy, ultrasound of the fetal kidneys and skull is recommended. Children whose mothers took ARA II should be carefully examined for arterial hypotension.

Hydrochlorothiazide

Experience with the use of hydrochlorothiazide during pregnancy, especially in the first trimester, is limited. Hydrochlorothiazide penetrates the BBB. Based on the pharmacological mechanism of action of hydrochlorothiazide, its use in the second and third trimesters can impair fetoplacental blood flow and cause jaundice, fluid and electrolyte imbalance and thrombocytopenia in the fetus/newborn. Hydrochlorothiazide should not be used to treat edema in pregnancy, hypertension in pregnancy or preeclampsia due to the risk of a decrease in blood volume and deterioration of placental blood flow without proper therapeutic effect on the course of the disease.

Hydrochlorothiazide should not be used to treat essential hypertension in pregnant women, except in rare cases when other treatment is not possible.

Breastfeeding period

Taking 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.

Contraindications

— cholestasis and obstructive diseases of the biliary tract;

– liver dysfunction;

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

– simultaneous use with drugs containing aliskiren in patients with diabetes mellitus or renal failure (GFR less than 60 ml/min/1.73 m2);

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

– refractory hypokalemia, hypercalcemia;

– hereditary fructose intolerance (contains sorbitol).

– pregnancy;

– period of breastfeeding;

– age under 18 years (efficacy and safety have not been established);

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

The drug should be prescribed with caution in case of bilateral renal artery stenosis or stenosis of the artery of a single kidney, severe renal dysfunction; a decrease in blood volume due to previous diuretic therapy, restriction of salt intake, diarrhea or vomiting; hyperkalemia; condition after kidney transplantation (no experience of use); chronic heart failure FC III-IV according to NYHA classification; stenosis of the aortic and mitral valves; idiopathic hypertrophic subaortic stenosis; hypertrophic obstructive cardiomyopathy; IHD and cerebrovascular diseases; diabetes mellitus; primary hyperaldosteronism; gout; disturbances of water and electrolyte balance (including hypokalemia, hyponatremia, hypochloremic alkalosis, hypomagnesemia); hyperuricemia; angle-closure glaucoma (due to the presence of hydrochlorothiazide in the composition); systemic lupus erythematosus; in patients of the Negroid race; elderly patients (over 70 years old).

Experience with use in patients with renal failure (creatinine clearance more than 30 ml/min) is limited, but does not confirm the development of side effects from the kidneys; dose adjustment is not required.

Side Effects

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

Telzap Plus 80 mg + 12.5 mg: the overall incidence of adverse reactions was comparable to that during monotherapy with telmisartan. The dependence of the development of adverse reactions on the dose of the drug has not been established; there was no relationship with the gender, age or race of patients.

Adverse reactions are divided into system-organ classes in accordance with MedDRA. The frequency of side effects was determined according to the WHO classification: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10,000, <1/1000), very rare (<1/10,000), including individual reports; frequency is unknown (it is not possible to determine the frequency of occurrence of a side effect based on available data).

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

From the immune system: rarely – increased symptoms or exacerbation of systemic lupus erythematosus (during post-registration surveillance).

From the side of metabolism and nutrition: infrequently – hypokalemia; rarely – hyperuricemia, hyponatremia.

Mental disorders: infrequently – anxiety; rarely – depression.

From the nervous system: often – dizziness; infrequently – fainting, paresthesia; rarely – insomnia, sleep disturbance.

On the part of the organ of vision: rarely – visual impairment, transient blurred vision.

On the part of the hearing organ: infrequently – vertigo.

From the cardiovascular system: infrequently – tachycardia, arrhythmia, arterial hypotension, orthostatic hypotension.

From the respiratory system: infrequently – shortness of breath; rarely – respiratory distress syndrome (including pneumonitis and pulmonary edema).

From the digestive system: infrequently – diarrhea, dry mouth, flatulence; rarely – abdominal pain, constipation, dyspepsia, vomiting, gastritis.

From the liver and biliary tract: rarely – impaired liver function, liver disease.

From the skin and subcutaneous tissues: rarely – angioedema (also fatal), erythema, itching, skin rash, increased sweating, urticaria.

From the musculoskeletal system and connective tissue: infrequently – back pain, muscle spasms, myalgia; rarely – joint pain, muscle spasms, pain in the limbs.

From the genital organs and breast: rarely – erectile dysfunction.

General disorders and disorders at the injection site: infrequently – chest pain; rarely – flu-like syndrome, pain.

From laboratory and instrumental studies: rarely – increased concentration of creatinine in the blood plasma, increased CPK activity, increased activity of liver transaminases.

Additional information about individual components

Side effects noted when using one of the components, the development of which can be expected when using a 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 reported in the placebo group (41.4% and 43.9%, respectively). The following adverse reactions were reported during a clinical trial of telmisartan, including a group of patients at high cardiovascular risk over the age of 50 years.

Infectious and parasitic diseases: uncommon – upper respiratory tract infections, urinary tract infections, including cystitis; rarely – sepsis, incl. with fatal outcome.

From the hematopoietic system: infrequently – anemia; rarely – eosinophilia, thrombocytopenia.

From the immune system: rarely – hypersensitivity reactions, anaphylactic reactions.

From the side of metabolism and nutrition: infrequently – hyperkalemia; rarely – hypoglycemia (in patients with diabetes).

From the nervous system: rarely – drowsiness.

From the cardiovascular system: infrequently – bradycardia.

From the respiratory system: infrequently – cough; very rarely – interstitial lung diseases.

From the digestive system: rarely – a feeling of discomfort in the stomach.

From the skin and subcutaneous tissues: rarely – eczema, drug rash, toxic skin rash.

From the musculoskeletal system: rarely – arthrosis, pain in the tendon area.

From the urinary system: rarely – impaired renal function (including acute renal failure).

General disorders and disorders at the injection site: uncommon – asthenia.

From laboratory and instrumental studies: rarely – decrease in hemoglobin content.

Hydrochlorothiazide

Hydrochlorothiazide may cause or worsen hypovolemia, which may lead to fluid and electrolyte imbalance. Adverse reactions reported with hydrochlorothiazide are listed below.

Infectious and parasitic diseases: frequency unknown – sialadenitis.

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

From the immune system: frequency unknown – anaphylactic reactions, hypersensitivity reactions.

From the endocrine system: frequency unknown – lack of adequate glycemic control in diabetes mellitus.

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

Mental disorders: frequency unknown – excited state.

From the nervous system: frequency unknown – presyncope.

From the organ of vision: frequency unknown – xanthopsia, acute myopia, acute angle-closure glaucoma.

From the side of blood vessels: frequency unknown – necrotizing vasculitis.

From the digestive system: frequency unknown – pancreatitis, feeling of discomfort in the stomach.

From the liver and biliary tract: frequency unknown – jaundice (parenchymal or cholestatic).

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

From the urinary system: frequency unknown – interstitial nephritis, renal dysfunction, glycosuria.

From the musculoskeletal system and connective tissue: frequency unknown – weakness.

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

From laboratory and instrumental studies: frequency unknown – hypertriglyceridemia, hypercholesterolemia, hyperglycemia.

Interaction

Double blockade of the RAAS

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

The simultaneous use of ACE inhibitors with ARB II or drugs containing aliskiren is characterized by an increased risk of developing arterial hypotension, hyperkalemia and decreased renal function (including acute renal failure) in patients compared to the use of each drug separately.

In patients with diabetic nephropathy, the use of a combination of ACE inhibitors and ARB II is contraindicated.

Digoxin

With simultaneous use of telmisartan with digoxin, an average increase in peak plasma concentration (49%) and trough concentration (20%) of digoxin was noted. When co-administered, at the beginning of treatment, when selecting a dose and stopping treatment with telmisartan, the concentration of digoxin in the blood should be monitored to maintain it within the therapeutic range.

Drugs that cause potassium loss and hypokalemia

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

Medicines that cause an increase in potassium levels in the blood plasma

Like other drugs that act on the RAAS, the use of the telmisartan/hydrochlorothiazide combination may cause hyperkalemia. The risk may increase when used concomitantly with other drugs that can cause hyperkalemia (salt substitutes containing potassium, potassium-sparing diuretics, ACE inhibitors, ARB II, NSAIDs, including selective COX-2 inhibitors, heparin, immunosuppressants (cyclosporine or tacrolimus) and trimethoprim).

If precautions are strictly followed, combination with ACE inhibitors or NSAIDs is associated with less risk.

If it is necessary to use these drugs simultaneously with the telmisartan/hydrochlorothiazide combination, it is recommended to monitor the potassium level in the blood plasma.

Lithium

With the simultaneous use of lithium preparations with ACE inhibitors and rarely with ARA II, including the combination of telmisartan/hydrochlorothiazide, a reversible increase in the concentration of lithium in the blood plasma and its toxic effect was observed. When used simultaneously with lithium preparations, it is recommended to carefully monitor the concentration of lithium in the blood plasma.

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 ARA II and weaken the diuretic, natriuretic effect of thiazide diuretics.

In some patients with impaired renal function (for example, in dehydrated patients with reduced volume of blood volume, elderly patients), the simultaneous use of ARB II and drugs that inhibit COX may lead to a further deterioration of renal function, up to the development of acute renal failure, which is usually reversible. Therefore, the simultaneous use of the combination of telmisartan/hydrochlorothiazide with NSAIDs should be used with caution, especially in elderly patients. It is necessary to ensure that patients receive adequate fluid intake, and renal function should be monitored at the beginning of simultaneous use and periodically thereafter.

When telmisartan was taken concomitantly with ibuprofen or paracetamol, no clinically significant interaction effect was observed.

Medicines whose action is affected by changes in plasma potassium levels

It is recommended to periodically monitor the potassium content in the blood plasma and conduct an ECG during use with drugs whose effect depends on changes in the concentration of potassium in the blood plasma (for example, with cardiac glycosides, antiarrhythmic drugs), as well as after an attack of ventricular tachycardia, incl. caused by drugs (including some antiarrhythmic drugs). Hypokalemia was a provoking factor for the development of ventricular tachycardia of the “pirouette” type (torsade de pointes):

– class IA antiarrhythmic drugs (for example, quinidine, hydroquinidine, disopyramide);

– class III antiarrhythmic drugs (for example, amiodarone, sotalol, dofetilide, ibutilide);

– some antipsychotics (for example, thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol);

– other drugs (for example, bepridil, cisapride, difemanil, erythromycin [IV injection], halofantrine, mizolastine, pentamidine, sparfloxacin, terfenadine, vincamine [IV injection]).

Cardiac glycosides

Hypokalemia or hypomagnesemia caused by hydrochlorothiazide may contribute to the occurrence of arrhythmia during therapy with cardiac glycosides.

Other antihypertensive drugs

Telmisartan may enhance the effect of other antihypertensive drugs.

Antidiabetic agents (oral medications and insulin)

Dosage adjustments of antidiabetic medications may be required.

Metformin

Metformin should be used with caution due to the risk of lactic acidosis caused by possible functional renal failure while taking hydrochlorothiazide.

Cholestyramine and colestipol

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

Pressor amines (eg, norepinephrine (norepinephrine))

The effect of vasopressor amines may be weakened.

Nondepolarizing skeletal muscle relaxants (eg, tubocurarine)

The effect of non-depolarizing muscle relaxants can be enhanced by hydrochlorothiazide.

Antigout medications (eg, probenecid, sulfinpyrazone, and allopurinol)

It may be necessary to adjust the dose of drugs that promote the removal of uric acid, since hydrochlorothiazide can increase the level of uric acid in the blood plasma. The dose of probenecid or sulfinpyrazone may need to be increased. Concomitant use of a thiazide diuretic may increase the incidence of hypersensitivity reactions to allopurinol.

Calcium salts

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

Due to their effect on calcium metabolism, thiazides may interfere with test results to assess parathyroid function.

β-adrenergic blockers and diazoxide

The hyperglycemic effect of β-adrenergic blockers and diazoxide can be enhanced by hydrochlorothiazide.

Anticholinergics (eg, atropine, biperiden)

Anticholinergics may increase the bioavailability of hydrochlorothiazide by decreasing gastrointestinal motility and gastric emptying rate.

Amantadine

Hydrochlorothiazide may increase the risk of adverse reactions caused by amantadine.

Glycyrrhizic acid

The interaction of hydrochlorothiazide and licorice root (glycyrrhizic acid) can lead to the development of hypokalemia.

Cytotoxic drugs (eg, cyclophosphamide, methotrexate)

Hydrochlorothiazide may reduce the renal excretion of cytotoxic drugs and enhance their myelosuppressive effect.

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 alcohol, barbiturates, narcotics, or antidepressants.

Corticosteroids (for systemic use)

Corticosteroids weaken the antihypertensive effect of telmisartan.

Overdose

No cases of overdose have been identified. Possible symptoms consist of symptoms of overdose of individual components.

Symptoms

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

An overdose of hydrochlorothiazide is associated with a decrease in electrolyte levels (hypokalemia, hypochloremia) and hypovolemia due to excessive diuresis. The most common symptoms of overdose are nausea and drowsiness. Hypokalemia may lead to muscle spasm and/or exacerbation of arrhythmias when used concomitantly with cardiac glycosides or certain antiarrhythmic drugs.

Treatment

Telmisartan is not eliminated by hemodialysis. The extent of hydrochlorothiazide elimination by hemodialysis has not been established. 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. The patient should be placed on his back, legs elevated. If necessary, it is recommended to replenish the bcc, for example, by intravenous administration of 0.9% sodium chloride solution. Sympathomimetic drugs may be prescribed.

Storage conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C.

Shelf life

2 years. Do not use after the expiration date stated on the package.

Manufacturer

Sanofi Ilac Sanayi ve Ticaret A.Ş., Türkiye