Telsartan N, tablets 12.5 mg+80 mg 28 pcs.

Pharmacodynamics

Telsartan® H is a combination of telmisartan (angiotensin II receptor antagonist) and hydrochlorothiazide, a thiazide diuretic. Simultaneous use of these components leads to a greater antihypertensive effect than the use of each of them separately.

Administration of Telsartan® H once daily results in a significant gradual decrease in blood pressure (BP).

Telmisartan

Telmisartan is a specific angiotensin receptor antagonist (ARA) II, effective when taken orally. It has high affinity to the AT1 subtype of angiotensin II receptors, through which the action of angiotensin II is realized.

It displaces angiotensin II from binding to the receptor without exhibiting agonist properties against this receptor. Telmisartan binds only to the AT1 subtype of the angiotensin II receptor. The binding is long-lasting.

It has no affinity for other receptors, including AT2 receptor and other less studied angiotensin receptors. The functional significance of these receptors as well as the effect of their possible overstimulation by angiotensin II, the concentration of which increases with telmisartan administration, has not been studied.

Telmisartan reduces plasma aldosterone concentration, does not inhibit plasma renin and does not block ion channels. Telmisartan does not inhibit angiotensin-converting enzyme (kininase II), which also catalyzes bradykinin degradation. Therefore, an increase in bradykinin-induced side effects is not expected.

In patients with arterial hypertension, telmisartan at a dose of 80 mg completely blocks the hypertensive effects of angiotensin II. The onset of antihypertensive action is observed within 3 hours after the first oral administration of telmisartan.

The action of the drug lasts for 24 hours and remains significant up to 48 hours. Expressed antihypertensive effect usually develops 4 weeks after regular drug intake.

In patients with arterial hypertension telmisartan reduces systolic and diastolic BP without affecting heart rate (HR).

In the case of abrupt telmisartan withdrawal, BP gradually returns to baseline levels without the development of “withdrawal” syndrome.

The study with telmisartan evaluated cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke or hospitalization due to chronic heart failure.

It has been shown to reduce cardiovascular morbidity and mortality in patients at high cardiovascular risk (with coronary artery disease, stroke, peripheral artery disease or diabetes with concomitant target organ damage such as retinopathy, left ventricular hypertrophy, macro- or microalbuminuria in the history) over 55 years of age.

Hydrochlorothiazide

Hydrochlorothiazide is a thiazide diuretic. Thiazide diuretics affect electrolyte reabsorption in the renal tubules by directly increasing sodium and chloride excretion (approximately equivalent amounts).

Diuretic effect of hydrochlorothiazide leads to a decrease in circulating blood volume (RBC), increased plasma renin activity, increased secretion of aldosterone with a subsequent increase in urinary potassium and hydrocarbonates and, consequently, a decrease in plasma potassium.

In concomitant administration with telmisartan there is a tendency to stop potassium loss caused by these diuretics, presumably due to blockade of renin-angiotensin-aldosterone system (RAAS).

After oral administration diuresis increases after 2 hours, and the maximum effect is observed after about 4 hours. The diuretic effect of the drug persists for approximately 6-12 hours.

Long-term use of hydrochlorthiazide reduces the risk of cardiovascular complications and mortality from them.

Maximum antihypertensive effect of Telsartan® N is usually achieved 4 weeks after the start of treatment.

Pharmacokinetics

The co-administration of Telmisartan and hydrochlorothiazide has no effect on the pharmacokinetics of either drug component.

Telmisartan

When taken orally, it is rapidly absorbed from the gastrointestinal tract.

Bioavailability is approximately 50%. Concentration peaks after about 0.5-1.5 hours. Administration with food decreases area under pharmacokinetic curve “concentration-time” (AUC) from 6% (with a dose of 40 mg) to 19% (with a dose of 160 mg). In 3 hours after oral administration, plasma concentrations level off regardless of food intake.

There is a difference in plasma concentrations of telmisartan in men and women. Maximum plasma concentrations (Cmax) are approximately 3 times and AUC approximately 2 times higher in women compared to men with no significant effect on efficacy. Nevertheless, increase of hypotensive effect is not observed in women.

The binding to plasma proteins is significant (more than 99.5%), mainly to albumin and alpha1-acid glycoprotein. The volume of distribution is approximately 500 liters.

Telmisartan is metabolized by conjugation with glucuronic acid. Metabolites are pharmacologically inactive. The elimination half-life (T1/2) is more than 20 hours. It is excreted unchanged in the intestine, renal excretion is less than 2%. Total plasma clearance is high (about 900 ml/min).

Elderly patients

Pharmacokinetics of telmisartan in elderly patients does not differ from younger patients. No dose adjustment is required.

Patients with renal impairment

No change in telmisartan dose is required in patients with renal impairment, including patients on hemodialysis. Telmisartan is not eliminated by hemodialysis.

Patients with hepatic impairment

Pharmacokinetic studies in patients with hepatic impairment have shown increased absolute bioavailability to nearly 100%. In patients with hepatic insufficiency the T1/2 is not changed (see section “Dosage and administration”).

Hydrochlorothiazide

After oral administration of Telsartan® H, the maximum plasma concentrations of hydrochlorothiazide are reached within 1-3 hours. Absolute bioavailability is about 60% (based on total renal excretion). Plasma proteins bind 64% of hydrochlorothiazide, and the volume of distribution is 0.8±0.3 l/kg.

Hydrochlorothiazide is not metabolized in the body and is excreted by the kidneys almost unchanged. About 60% of the oral dose is eliminated within 48 hours. Renal clearance is about 250-300 ml/min. T1/2 of hydrochlorothiazide is 10-15 hours.

There is a difference in plasma concentrations in men and women. In women telmisartan plasma concentrations are 2-3 times higher than in men; also in women there is a tendency for clinically insignificant increase in plasma concentrations of hydrochlorothiazide.

Patients with renal impairment

In patients with impaired renal function the excretion rate of hydrochlorothiazide is reduced.
Studies conducted with patients with a creatinine clearance of 90 ml/min have shown that the T1/2 of hydrochlorothiazide is increased. In patients with decreased renal function, the T1/2 is approximately 34 hours.

Indications

Arterial hypertension (in case of ineffectiveness of telmisartan or hydrochlorothiazide in monotherapy).

Pharmacological effect

Pharmacodynamics

Telsartan® N is a combination of telmisartan (angiotensin II receptor antagonist) and hydrochlorothiazide, a thiazide diuretic. The simultaneous use of these components leads to a greater antihypertensive effect than the use of each of them separately.

Taking Telsartan® N once a day leads to a significant gradual decrease in blood pressure (BP).

Telmisartan

Telmisartan is a specific angiotensin receptor antagonist (ARA) II, effective when taken orally. It has a high affinity for the AT1 subtype of angiotensin II receptors, through which the action of angiotensin II is realized.

Displaces angiotensin II from its connection with the receptor, without exhibiting agonist properties in relation to this receptor. Telmisartan binds only to the AT1 subtype of angiotensin II receptors. The connection is long-term.

It has no affinity for other receptors, including the AT2 receptor and other, less studied angiotensin 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 concentrations, does not inhibit plasma renin and does not block ion channels. Telmisartan does not inhibit angiotensin-converting enzyme (kininase II), which also catalyzes the degradation of bradykinin. Therefore, an increase in the side effects caused by bradykinin is not expected.

In patients with arterial hypertension, telmisartan at a dose of 80 mg completely blocks the hypertensive effect of angiotensin II. The onset of antihypertensive action is observed within 3 hours after the first oral administration of telmisartan.

The effect of the drug lasts for 24 hours and remains significant for up to 48 hours. A pronounced antihypertensive effect usually develops 4 weeks after regular use of the drug.

In patients with arterial hypertension, telmisartan reduces systolic and diastolic blood pressure without affecting heart rate (HR).

In case of abrupt withdrawal of telmisartan, blood pressure gradually returns to the initial level without the development of withdrawal syndrome.

The telmisartan study assessed incidence of cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, or hospitalization due to chronic heart failure.

It has been shown to reduce cardiovascular morbidity and mortality in patients at high cardiovascular risk (with coronary artery disease, stroke, peripheral artery disease, or diabetes mellitus with concomitant end-organ damage such as retinopathy, left ventricular hypertrophy, history of macro- or microalbuminuria) over the age of 55 years.

Hydrochlorothiazide

Hydrochlorothiazide is a thiazide diuretic. Thiazide diuretics affect the reabsorption of electrolytes in the renal tubules, directly increasing the excretion of sodium and chloride (in approximately equivalent amounts).

The diuretic effect of hydrochlorothiazide leads to a decrease in circulating blood volume (CBV), an increase in the activity of plasma renin, an increase in the secretion of aldosterone with a subsequent increase in the content of potassium and bicarbonates in the urine and, as a consequence, a decrease in the content of potassium in the blood plasma.

When taken concomitantly with telmisartan, there is a tendency to reverse the potassium loss caused by these diuretics, presumably due to blockade of the renin-angiotensin-aldosterone system (RAAS).

After oral administration, diuresis increases after 2 hours, and the maximum effect is observed after approximately 4 hours. The diuretic effect of the drug lasts for approximately 6-12 hours.

Long-term use of hydrochlorothiazide reduces the risk of complications of cardiovascular diseases and mortality from them.

The maximum antihypertensive effect of Telsartan® N is usually achieved 4 weeks after the start of treatment.

Pharmacokinetics

The combined use of telmisartan and hydrochlorothiazide does not affect the pharmacokinetics of each of the components of the drug.

Telmisartan

When taken orally, it is quickly absorbed from the gastrointestinal tract.

Bioavailability – approximately 50%. Peak concentration occurs after approximately 0.5-1.5 hours. When taken simultaneously with food, the decrease in the area under the concentration-time pharmacokinetic curve (AUC) ranges from 6% (when taking a dose of 40 mg) to 19% (when taking a dose of 160 mg). 3 hours after oral administration, the concentration in the blood plasma levels off regardless of food intake.

There is a difference in plasma concentrations of telmisartan in men and women. The maximum plasma concentration (Cmax) is approximately 3-fold and the AUC is approximately 2-fold higher in women compared to men, with no significant effect on efficacy. However, an increase in the hypotensive effect is not observed in women.

The connection with blood plasma proteins is significant (more than 99.5%), mainly with albumin and alpha1-acid glycoprotein. Distribution volume approx. 500 liters.

Telmisartan is metabolized by conjugation with glucuronic acid. Metabolites are pharmacologically inactive. The half-life (T1/2) is more than 20 hours. Excreted through the intestines unchanged, excretion by the kidneys is less than 2%. The total plasma clearance is high (about 900 ml/min).

Elderly patients

The pharmacokinetics of telmisartan in elderly patients does not differ from young patients. No dose adjustment is required.

Patients with renal failure

No dose adjustment of telmisartan is required in patients with renal failure, including patients on hemodialysis. Telmisartan is not removed by hemodialysis.

Patients with liver failure

Pharmacokinetic studies in patients with liver failure showed an increase in absolute bioavailability to almost 100%. In case of liver failure, T1/2 does not change (see section “Method of administration and dosage”).

Hydrochlorothiazide

After oral administration of Telsartan® N, maximum concentrations of hydrochlorothiazide in the blood plasma are achieved within 1-3 hours. Absolute bioavailability is approximately 60% (based on total renal excretion). 64% of hydrochlorothiazide is bound to blood plasma proteins, and the volume of distribution is 0.8±0.3 l/kg.

Hydrochlorothiazide is not metabolized in the body and is excreted by the kidneys almost unchanged. About 60% of an ingested dose is eliminated within 48 hours. Renal clearance is about 250-300 ml/min. T1/2 of hydrochlorothiazide is 10-15 hours.

There is a difference in plasma concentrations between men and women. In women, the plasma concentration of telmisartan is 2-3 times higher than in men; Also in women there is a tendency to a clinically insignificant increase in plasma concentrations of hydrochlorothiazide.

Patients with renal failure

In patients with impaired renal function, the rate of elimination of hydrochlorothiazide is reduced.
Studies conducted in patients with a creatinine clearance of 90 ml/min have shown that T1/2 of hydrochlorothiazide increases. In patients with reduced renal function, T1/2 is about 34 hours.

Special instructions

Conditions that contribute to increased RAAS activity

In some patients, due to suppression of the activity of the RAAS, especially with the simultaneous administration of drugs acting on this system, renal function is impaired (including acute renal failure).

Therefore, therapy accompanied by such dual blockade of the RAAS (for example, by adding an angiotensin-converting enzyme inhibitor (ACEI) or a direct renin inhibitor-aliskiren to angiotensin II receptor antagonists) should be carried out strictly individually and with regular monitoring of renal function, including periodic monitoring of serum potassium and creatinine levels.

The use of thiazide diuretics in patients with impaired renal function can lead to azotemia. Periodic monitoring of renal function is recommended.

Renovascular hypertension

In patients with bilateral renal artery stenosis or arterial stenosis of a single functioning kidney, when using medications that affect the RAAS, the risk of developing severe arterial hypotension and renal failure increases.

Liver dysfunction

In patients with impaired liver function or progressive liver disease, a drug containing hydrochlorothiazide and telmisartan should be used with caution, since even slight changes in the water and electrolyte balance may contribute to the development of hepatic coma.

Effect on metabolism and function of endocrine glands

In patients with diabetes mellitus, changes in the dose of insulin or oral hypoglycemic agents may be required. During therapy with thiazide diuretics, latent diabetes mellitus may manifest itself.

In some cases, when using thiazide diuretics, hyperuricemia and exacerbation of gout may develop.

Diabetes mellitus

In patients with diabetes mellitus and additional cardiovascular risk, such as patients with diabetes mellitus and coronary artery disease (CAD), the risk of myocardial infarction and sudden cardiovascular death may be increased when taking blood pressure-lowering drugs such as angiotensin II receptor antagonists (ARAs) or ACE inhibitors.

In patients with diabetes mellitus, CAD may be asymptomatic and therefore may be undiagnosed. In patients with diabetes mellitus, before starting the use of a drug containing hydrochlorothiazide and telmisartan, appropriate diagnostic tests, including an exercise test, should be performed to identify and treat coronary artery disease.

Acute myopia and secondary angle-closure glaucoma

Hydrochlorothiazide, being a sulfonamide derivative, can cause an idiosyncratic reaction in the form of acute transient myopia and acute angle-closure glaucoma.

Symptoms of these disorders include a sudden decrease in visual acuity or eye pain, which typically occurs within a few hours to several weeks after starting to use the drug. If left untreated, acute angle-closure glaucoma can lead to vision loss. The main treatment is to discontinue hydrochlorothiazide as quickly as possible.

It is important to keep in mind that if intraocular pressure remains uncontrolled, emergency medical or surgical treatment may be required. Risk factors for the development of acute angle-closure glaucoma include a history of allergies to sulfonamides or penicillin.

Water-electrolyte balance disorders

When using a drug containing hydrochlorothiazide and telmisartan, as in the case of diuretic therapy, periodic monitoring of the content of electrolytes in the blood serum is necessary. Thiazide diuretics, including hydrochlorothiazide, can cause disturbances in water-electrolyte balance and acid-base status (hypokalemia, hyponatremia and hypochloremic alkalosis).

Warning signs for these disorders are dryness of the oral mucosa, a feeling of thirst, general weakness, drowsiness, anxiety, myalgia or convulsive twitching of the calf muscles, muscle weakness, a marked decrease in blood pressure, oliguria, tachycardia and gastrointestinal disorders such as nausea or vomiting.

When using thiazide diuretics, hypokalemia may develop, but simultaneous use of telmisartan may increase the level of potassium in the blood. The risk of hypokalemia increases most in patients with liver cirrhosis, with increased diuresis, while following a salt-free diet, as well as in case of simultaneous use with glucocorticosteroids, calcitonin, ACTH (adrenocortitropic hormone), glycyrrhizic acid (found in licorice root).

Telmisartan, which is part of the drug Telsartan®, on the contrary, can lead to hyperkalemia due to antagonism of angiotensin II receptors (AT1 subtype). Although clinically significant hyperkalemia has not been reported with the combination of hydrochlorothiazide and telmisartan, risk factors for its development include renal and/or heart failure and diabetes mellitus.

There is no evidence that a product containing hydrochlorothiazide and telmisartan can reduce or prevent diuretic-induced hyponatremia. Hypochloremia is usually minor and does not require treatment.

Thiazide diuretics can reduce the excretion of calcium by the kidneys and cause (in the absence of obvious disturbances in calcium metabolism) a transient and slight increase in serum calcium. More severe hypercalcemia may be a sign of hidden hyperparathyroidism.

Before assessing parathyroid function, thiazide diuretics should be discontinued. Thiazide diuretics have been shown to increase renal excretion of magnesium, which may lead to hypomagnesemia.

In patients with coronary heart disease, the use of any antihypertensive drug, in case of excessive reduction in blood pressure, can lead to myocardial infarction or stroke.

Increased monitoring of patients with impaired uric acid metabolism is required; Thiazides can reduce the amount of iodine that binds to serum proteins without showing signs of thyroid dysfunction; There is information about cases of the development of photosensitivity when taking thiazide diuretics.

If a photosensitivity reaction occurs during treatment, it is recommended to suspend treatment. If it is decided that it is necessary to resume taking a diuretic, it is necessary to protect areas of the body that may be exposed to sunlight or ultraviolet A rays and avoid sun exposure; hydrochlorothiazide may increase the concentration of cholesterol and triglycerides in the blood; hydrochlorothiazide may give a positive result during doping control.

There are reports of the development of systemic lupus erythematosus with the use of thiazide diuretics.
Telsartan® N can, if necessary, be used in conjunction with other antihypertensive drugs.

Drugs containing hydrochlorothiazide and telmisartan are less effective in black patients.
No special clinical studies have been conducted to evaluate the effect of the drug Telsartan® N on the ability to drive vehicles and operate mechanisms that require increased attention.

However, when driving vehicles and engaging in hazardous activities, the possibility of dizziness and drowsiness should be taken into account, which requires caution.

Active ingredient

Hydrochlorothiazide, Telmisartan

Composition

1 tablet 12.5 mg+80 mg contains:

Active ingredients:
hydrochlorothiazide 12.50 mg
telmisartan 80.00 mg
Excipients:
meglumine,
sodium hydroxide,
povidone K30,
polysorbate-80,
mannitol,
lactose monohydrate,
magnesium stearate,
red iron oxide dye (E172).

Pregnancy

The use of Telsartan® N is contraindicated during pregnancy.

Telmisartan

The use of angiotensin II receptor antagonists during the first trimester of pregnancy is not recommended and these drugs should not be prescribed during pregnancy. If pregnancy is diagnosed, the drug should be stopped immediately.

If necessary, alternative therapy (other classes of antihypertensive drugs approved for use during pregnancy) should be used.

The use of angiotensin II receptor antagonists during the second and third trimesters of pregnancy is contraindicated.

In preclinical studies of telmisartan, no teratogenic effect was noted, but fetotoxicity was established.

Exposure to angiotensin II receptor antagonists during the second and third trimesters of pregnancy is known to cause fetotoxicity in humans (decreased renal function, oligohydramnios, delayed ossification of the skull bones), as well as neonatal toxicity (renal failure, hypotension, hyperkalemia).

Patients planning pregnancy should be given alternative therapy. If treatment with angiotensin II receptor antagonists occurred during the second trimester of pregnancy, it is recommended to perform an ultrasound examination of the fetal kidneys and skull bones.

Infants whose mothers received angiotensin II receptor antagonists should be closely monitored for hypotension.

Hydrochlorothiazide

Experience with the use of hydrochlorothiazide during pregnancy, especially during the first trimester, is limited.
Hydrochlorothiazide penetrates the placental barrier.

Given the pharmacological mechanism of action of hydrochlorothiazide, it is assumed that its use during the second and third trimesters of pregnancy may interfere with fetoplacental perfusion and cause changes in the embryo and fetus such as jaundice, fluid and electrolyte imbalance and thrombocytopenia.

Hydrochlorothiazide should not be used for edema in pregnancy, hypertension in pregnancy or during preeclampsia, as there is a risk of decreased plasma volume and decreased placental perfusion, and there is no beneficial effect in these clinical situations.

Hydrochlorothiazide should not be used to treat essential hypertension in pregnancy, except in rare situations where other treatments cannot be used.

Therapy with Telsartan® N is contraindicated during breastfeeding.

In animal studies, no effect of telmisartan and hydrochlorothiazide on fertility was observed. No studies have been conducted on the effects on human fertility.

Contraindications

Hypersensitivity to active substances or auxiliary components of the drug or other sulfonamide derivatives.
Obstructive diseases of the biliary tract.
Severe liver dysfunction (class C on the Child-Pugh scale).
Severe renal impairment (creatinine clearance less than 30 ml/min).
Refractory hypokalemia, hypercalcemia.
Concomitant use with aliskiren and drugs containing aliskiren in patients with diabetes mellitus and/or moderate or severe renal impairment (glomerular filtration rate (GFR) less than 60 ml/min/1.73 m2 body surface area).
Concomitant use with angiotensin-converting enzyme (ACE) inhibitors in patients with diabetic nephropathy.
Lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome.
Pregnancy.
Breastfeeding period.
Age up to 18 years (efficacy and safety have not been established).
With caution:
Bilateral renal artery stenosis or stenosis of the artery of a single kidney (see section “Special instructions”).
Impaired liver function or progressive liver disease (Class A and B on the Child-Pugh scale) (see section “Special Instructions”).
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 (CHF) III-IV functional class (FC) according to the New York Heart Association (NYHA) classification.
Hypercalcemia.
Hypercholesterolemia.
Hypertriglyceridemia.
Coronary heart disease.
Progressive liver diseases (risk of developing hepatic coma).
Stenosis of the aortic and mitral valve.
Idiopathic hypertrophic subaortic stenosis.
Hypertrophic obstructive cardiomyopathy (HOCM).
Diabetes mellitus.
Primary aldosteronism.
Gout, hyperuricemia.
Systemic lupus erythematosus.
Secondary angle-closure glaucoma (due to the presence of hydrochlorothiazide in the composition).
Use in patients of the Negroid race.
Experience 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 and dose adjustment is not required.

Side Effects

Side effects reported with the combination of telmisartan and hydrochlorothiazide

The overall incidence of adverse events reported with the combination of telmisartan and hydrochlorothiazide was comparable to the incidence of adverse effects observed with telmisartan monotherapy in controlled trials involving 1471 patients randomized to telmisartan + hydrochlorothiazide (835 patients) or telmisartan alone (636).

The dependence of side effects on the dose, gender, age or race of patients has not been established.

All side effects that occur when using the combination of telmisartan and hydrochlorothiazide with a frequency exceeding the frequency of placebo (p≤0.05) are presented below according to system-organ classes.

Frequency of occurrence: very common (≥1/10); often (≥1/100 – <1/10); uncommon (≥1/1000 - <1/100); rare (≥1/10000 - <1/1000); very rare (< 1/10000); frequency unknown (cannot be determined from available data). Adverse reactions are presented in descending order of severity.Infectious and parasitic diseasesRarely: bronchitis, pharyngitis, sinusitis.
Immune system disorders
Rare: exacerbation or worsening of symptoms of systemic lupus erythematosus1.

Metabolic and nutritional disorders
Uncommon: hypokalemia.
Rarely: hyperuricemia, hyponatremia.

Mental disorders
Uncommon: anxiety.
Rarely: depression.

Nervous system disorders
Common: dizziness.
Uncommon: syncope/syncope, paresthesia.
Rarely: insomnia, sleep disorders.

Visual disorders
Rare: visual impairment, transient blurred vision.

Hearing and labyrinth disorders
Uncommon: vertigo.

Cardiac disorders
Uncommon: tachycardia, arrhythmia.

Vascular disorders
Uncommon: hypotension, orthostatic hypotension.

Disorders of the respiratory system, chest and mediastinal organs
Uncommon: shortness of breath.
Rare: respiratory distress syndrome (including pneumonia and non-cardiogenic pulmonary edema).

Gastrointestinal disorders
Uncommon: diarrhea, dry mouth, flatulence.
Rarely: abdominal pain, constipation, dyspepsia, vomiting, gastritis.

Disorders of the liver and biliary tract
Rare: liver dysfunction2.

Disorders of the skin and subcutaneous tissues
Rare: angioedema (including fatal cases), erythema, pruritus, rash, increased sweating, urticaria.

Musculoskeletal and connective tissue disorders
Uncommon: back pain, muscle spasms, myalgia.
Rarely: arthralgia, muscle cramps, pain in the calf muscles.

Disorders of the genital organs and breast
Uncommon: erectile dysfunction.

General disorders and disorders at the injection site
Uncommon: chest pain.
Rare: flu-like syndrome, pain.

Laboratory and instrumental data
Uncommon: increased concentration of uric acid in blood plasma.
Rarely: increased concentration of creatinine in blood plasma, increased activity of creatine phosphokinase in blood plasma, increased activity of liver enzymes.

1 – based on post-marketing experience.
2 – see subsection “Description of individual adverse reactions”.

Additional information on experience with individual active ingredients

Adverse reactions previously observed with each component of the drug may potentially occur with the combination of telmisartan and hydrochlorothiazide, even if they were not observed when studying this combination.

Telmisartan

The incidence of side effects with telmisartan is similar to that with placebo.
In placebo-controlled studies, the overall incidence of side effects observed with telmisartan (41.4%) was generally comparable to the incidence of side effects observed with placebo (43.9%).

The following side effects are based on the results of all clinical studies involving patients receiving telmisartan for hypertension or the results of the use of telmisartan in patients 50 years of age and older with a high risk of developing cardiovascular events.

Infectious and parasitic diseases

Uncommon: upper respiratory tract infections, urinary tract infections, including cystitis.
Rare: sepsis, including fatal cases.

Blood and lymphatic system disorders
Uncommon: anemia.
Rare: eosinophilia, thrombocytopenia.

Immune system disorders
Rarely: hypersensitivity reactions, anaphylactic reactions.

Metabolic and nutritional disorders
Uncommon: hyperkalemia.
Rare: hyperglycemia (in patients with diabetes mellitus).

Cardiac disorders
Uncommon: bradycardia.

Nervous system disorders
Rarely: drowsiness.

Disorders of the respiratory system, chest and mediastinal organs
Uncommon: cough.
Very common: interstitial lung disease3.

Gastrointestinal disorders
Rarely: feeling of discomfort in the stomach.

Disorders of the skin and subcutaneous tissues
Rare: eczema, drug and toxic rash.

Musculoskeletal and connective tissue disorders
Rarely: arthrosis, tendon pain.

Renal and urinary tract disorders
Uncommon: renal impairment (including acute renal failure).

General disorders and disorders at the injection site
Uncommon: asthenia.

Laboratory and instrumental data
Rare: decreased hemoglobin level.

3 – see subsection “Description of individual adverse reactions”.

Hydrochlorothiazide

The use of hydrochlorothiazide may lead to or worsen hypovolemia, which may cause electrolyte imbalance.

The following are the adverse reactions noted when using hydrochlorothiazide in monotherapy. The frequency of occurrence of such reactions cannot be determined.

Infectious and parasitic diseases
Sialadenitis.

Blood and lymphatic system disorders
Aplastic anemia, hemolytic anemia, bone marrow dysfunction, leukopenia, neutropenia, agranulocytosis, thrombocytopenia.

Immune system disorders
Anaphylactic reactions, hypersensitivity.

Endocrine system disorders
Uncontrolled diabetes mellitus.

Metabolic and nutritional disorders
Anorexia, loss of appetite, electrolyte imbalance, hypercholesterolemia, hyperglycemia, hypovolemia.

Mental disorders
Restlessness.

Nervous system disorders
Slight dizziness.

Visual disorders
Xanthopsia, acute myopia, acute angle-closure glaucoma.

Vascular disorders
Necrotizing vasculitis.

Gastrointestinal disorders
Pancreatitis, feeling of discomfort in the stomach.

Disorders of the liver and biliary tract
Hepatic jaundice, cholestatic jaundice.

Disorders of the skin and subcutaneous tissues
Lupus-like syndrome, photosensitivity reactions, cutaneous vasculitis, toxic epidermal necrolysis.

Musculoskeletal and connective tissue disorders
Weakness.

Renal and urinary tract disorders
Interstitial nephritis, renal dysfunction, glycosuria.

General disorders and disorders at the injection site
Pyrexia.
Laboratory and instrumental data
Increased triglyceride levels.
Description of selected adverse reactions

Liver dysfunction
Most cases of liver dysfunction with post-registration use of telmisartan have been described in patients in Japan. Apparently, these undesirable effects are more typical for this group of patients.

Sepsis

In the PRoFESS study, an increased incidence of sepsis was observed with telmisartan compared with placebo. The data obtained can be considered a random find, since the mechanism of the relationship is unknown.

Interstitial lung disease

Cases of interstitial lung disease were recorded during post-registration use of telmisartan and coincided with the period of its prescription. However, a cause-and-effect relationship between these events has not been established.

Interaction

Telmisartan

Antihypertensive drugs

The antihypertensive effect may be enhanced. In one study, a 2.5-fold increase in the AUC0-24 and Cmax of ramipril and ramiprilat was observed with the combined use of telmisartan and ramipril. The clinical significance of this interaction has not been established.

In the analysis of adverse events leading to discontinuation of treatment and the analysis of serious adverse events obtained during the clinical trial, it was found that cough and angioedema were more often observed with ramipril therapy, while arterial hypotension was more common with telmisartan therapy.

Cases of hyperkalemia, renal failure, arterial hypotension and syncope were observed significantly more often with the combined use of telmisartan and ramipril.

Lithium preparations

There was a reversible increase in the concentration of lithium in the blood plasma, accompanied by toxic effects when taking ACE inhibitors.

In rare cases, such changes have been reported with the use of angiotensin II receptor antagonists, in particular telmisartan. When using lithium preparations and angiotensin II receptor antagonists simultaneously, it is recommended to determine the lithium content in the blood.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs, including acetylsalicylic acid in doses used as an anti-inflammatory agent, cyclooxygenase-2 (COX-2) inhibitors and non-selective NSAIDs, can cause the development of acute renal failure in patients with reduced blood volume. Drugs that affect the RAAS may have a synergistic effect.

In patients receiving NSAIDs and telmisartan, blood volume should be compensated and renal function monitored at the beginning of treatment.

Reducing the effect of antihypertensive drugs such as telmisartan by inhibition
The vasodilatory effect of prostaglandins was observed when used together with NSAIDs. No clinically significant effect was observed when telmisartan was taken concomitantly with ibuprofen or paracetamol.

Digoxin, warfarin, hydrochlorothiazide, glibenclamide, simvastatin and amlodipine

No clinically significant interaction was identified. There was an increase in the average concentration of digoxin in the blood plasma by an average of 20% (in one case by 39%). When using telmisartan and digoxin simultaneously, it is advisable to periodically determine the concentration of digoxin in the blood plasma.

Aliskiren, aliskiren-containing drugs

Clinical data have shown that dual blockade of the RAAS, through concomitant use with ACE inhibitors, angiotensin II receptor blockers or aliskiren, is associated with a high incidence of side effects such as hypotension, hyperkalemia, decreased renal function (including acute renal failure), compared with the use of a single active RAAS blocker.

Hydrochlorothiazide

Ethanol, barbiturates or narcotic analgesics
Risk of orthostatic hypotension.

Oral hypoglycemic agents and insulin

Dosage adjustments of oral hypoglycemic agents and insulin may be required.

Metformin

Risk of developing lactic acidosis.

Cholestyramine and colestipol

In the presence of anion exchange resins, the absorption of hydrochlorothiazide is impaired.

Cardiac glycosides

Risk of hypokalemia or hypomagnesemia caused by thiazide diuretics, development of arrhythmias caused by taking cardiac glycosides.

Pressor amines (eg, norepinephrine)

The effect of pressor amines may be weakened.

Non-depolarizing muscle relaxants (for example, tubocurarine chloride)

Hydrochlorothiazide may enhance the effect of non-depolarizing muscle relaxants.

Antigout drugs

Serum uric acid concentrations may increase and therefore dose adjustments of uricosuric agents may be required. The use of thiazide diuretics increases the incidence of hypersensitivity reactions to allopurinol.

Calcium supplements and vitamin D

Thiazide diuretics may increase serum calcium levels due to decreased renal excretion. If you need to use calcium supplements, you should regularly monitor the calcium level in the blood serum and, if necessary, change the dose of calcium supplements.

Beta blockers and diazoxide

Thiazide diuretics may potentiate the hyperglycemia caused by beta-blockers and diazoxide.
M-anticholinergics (for example, atropine, biperidine)

Reduced gastrointestinal motility, increased bioavailability of thiazide diuretics.

Amantadine

Amantadine clearance may be decreased by hydrochlorothiazide, resulting in increased amantadine plasma concentrations and possible toxicity.

Cytotoxic agents (eg, cyclophosphamide, methotrexate)

Reducing the renal excretion of cytotoxic drugs and enhancing their myelosuppressive effect.
NSAIDs

Concomitant use with thiazide diuretics may lead to a decrease in diuretic and antihypertensive effect.

Drugs that lead to potassium excretion and hypokalemia

Drugs such as diuretics that remove potassium; laxatives; glucocorticosteroids; calcitonin; adrenocorticotropic hormone (ACTH); glycyrrhizic acid (found in licorice root); amphotericin B; carbenoxolone; benzylpenicillin; acetylsalicylic acid derivatives: may lead to increased hypokalemic effects. Hypokalemia caused by hydrochlorothiazide is compensated by the potassium-sparing effect of telmisartan.

Theophylline

Increased risk of hypokalemia.

Amiodarone

Concomitant use with thiazide diuretics may lead to an increased risk of arrhythmias associated with hypokalemia.

Potassium-sparing diuretics, potassium supplements, other drugs that can increase serum potassium levels (for example, heparin)

These remedies, as well as replacing sodium in table salt with potassium salts, can lead to hyperkalemia.

It is recommended to periodically monitor the potassium content in the blood plasma when using Telsartan® N simultaneously with drugs that can cause hypokalemia, as well as with drugs that can increase the potassium content in the blood serum.

Overdose

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

Telmisartan – marked decrease in blood pressure, tachycardia, bradycardia.

Hydrochlorothiazide – disturbances in the water-electrolyte balance of the blood (hypokalemia, hypochloremia), a decrease in blood volume, which can lead to muscle spasms and/or increase disorders of the cardiovascular system: arrhythmias caused by the simultaneous use of cardiac glycosides or certain antiarrhythmic drugs.

Treatment: symptomatic therapy, hemodialysis is ineffective. The extent to which hydrochlorothiazide is removed during hemodialysis has not been established. Regular monitoring of electrolyte levels and serum creatinine concentrations is necessary.

Storage conditions

At a temperature not exceeding 25 °C.

Keep out of the reach of children!

Shelf life

1 year

Manufacturer

Dr. Reddy’s Laboratories Ltd, India