Telmista H 80mg+12.5mg pills, 84pcs

Composition

for 1 tablet 12.5 mg + 40 mg/12.5 mg + 80 mg/25 mg + 80 mg

Active ingredients:

Hydrochlorothiazide 12.50 mg/12.50 mg/25.00 mg

Telmisartan 40.00 mg/80.00 mg/80.00 mg

Auxiliary substances:

Meglumine, sodium hydroxide, povidone-30, lactose monohydrate, sorbitol, magnesium stearate, mannitol, mannitol DC, dye iron oxide yellow (E 172) (for tablets 25 mg + 80 mg), dye iron oxide red (E 172) (for tablets 12.5 mg + 40 mg and 12.5 mg + 80 mg), hyprolose, silica colloidal anhydrous, sodium fumarate

drugs act

antihypertensive combo (diuretic + angiotensin II receptor antagonist)

Clinical Pharmacology

Pharmacodynamics

Telmista ® H is a combination of telmisartan (an angiotensin II receptor antagonist [ARA II]) and hydrochlorothiazide (a thiazide diuretic). The simultaneous use of these components leads to a more pronounced antihypertensive effect than the use of each of them separately.

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

Hydrochlorothiazide

The mechanism of action of thiazide diuretics (thiazides) is not fully understood. Thiazides block the reabsorption of sodium and chlorine ions at the beginning of the renal tubules. Thus, they increase the excretion of sodium and chlorine and, consequently, the elimination of water from the body.

As a result of the diuretic effect of hydrochlorothiazide, the volume of circulating blood (BCC) decreases, which increases the activity of renin and the content of aldosterone in blood plasma. This leads to an increase in the excretion of potassium ions by the kidneys and a decrease in the content of potassium in the blood plasma (hypokalemia). Hydrochlorothiazide also increases the excretion of magnesium ions and reduces the excretion of calcium ions by the kidneys. Thiazide diuretics reduce uric acid excretion by the kidneys and increase its concentration in blood plasma.

Thiazide diuretics also reduce carbonic anhydrase activity by increasing the elimination of bicarbonate ions. But this effect is usually weak and does not affect the pH of urine.

At maximum therapeutic doses, the diuretic / natriuretic effect of all thiazide diuretics is approximately the same. Natriuresis and diuresis occur within 2 hours and reach their maximum in about 4 hours. The duration of diuretic action of hydrochlorothiazide is from 6 to 12 hours.

Hydrochlorothiazide has an antihypertensive effect. Thiazide diuretics do not affect normal blood pressure.

Telmisartan

Telmisartan-specific ARA II (subtype AT₁), 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 binding to the receptor, without showing agonist properties with respect to this receptor. Telmisartan binds only to the AT1 subtype of angiotensin II receptors. The relationship is long-term. It has no affinity for other receptors, including AT₂ receptors and other less well-studied angiotensin receptors. The functional significance of these receptors, as well as the effect of their possible overstimulation with angiotensin II, the concentration of which increases with the use of telmisartan, have not been studied. Telmisartan reduces the concentration of aldosterone in the blood plasma, does not inhibit renin in the blood plasma and does not block ion channels. Telmisartan does not inhibit the angiotensin-converting enzyme (ACE) (kininase II), an enzyme that also breaks down bradykinin. 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 effect of angiotensin II. The onset of antihypertensive action is noted within 3 hours after the first oral use of telmisartan. The suppressive effect lasts for more than 24 hours and lasts up to 48 hours. A pronounced antihypertensive effect usually develops 4 weeks after regular use of telmisartan.

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

In the case of abrupt withdrawal of telmisartan, blood pressure gradually returns to its original level without the development of “withdrawal”syndrome.

The telmisartan trial evaluated cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for chronic heart failure (CHF). A reduction in cardiovascular morbidity and mortality has been shown in patients at high cardiovascular risk (with a history of coronary artery disease, stroke, peripheral artery disease, or diabetes mellitus with concomitant target organ damage, such as retinopathy, left ventricular hypertrophy, macro-or microalbuminuria) over the age of 55 years.

The maximum antihypertensive effect of Telmista ® H is usually achieved 4-8 weeks after the start of treatment.

Pharmacokinetics

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

Hydrochlorothiazide

Suction and distribution

Hydrochlorothiazide is not fully absorbed, but it is rapidly absorbed from the gastrointestinal tract (GIT). After oral use at a dose of 100 mg, the maximum concentration (cmax) of hydrochlorothiazide in blood plasma is reached in 1.5-2.5 hours. At the maximum diuretic activity (approximately 4 hours after oral use), the concentration of hydrochlorothiazide in blood plasma is 2 mcg / ml. The binding to plasma proteins is 40%.

Hydrochlorothiazide penetrates the placental barrier and is excreted in breast milk, but does not cross the blood-brain barrier.

Metabolism

Hydrochlorothiazide is not metabolized in the human body.

Deduction

The primary route of excretion by the kidneys (filtration and secretion) in unchanged form. Approximately 61% of the oral dose is eliminated within 24 hours. In patients with normal renal function, the half-life (_half-life) is from 5.6 to 14.8 hours (average 6.4 hours).

Special patient groups

Impaired renal function

In patients with moderate renal insufficiency, the_half-life of hydrochlorothiazide is on average 11.5 hours, and in patients with creatinine clearance (CC) less than 30 ml / min-20.7 hours.

Telmisartan

Suction

Telmisartan is rapidly absorbed, but the amount of drug absorbed may vary. The average absolute bioavailability of telmisartan is approximately 50%. When taking telmisartan with food, there is a decrease in the area under the concentration-time curve (AUC) from approximately 6% (when taking telmisartan at a dose of 40 mg per day) to 19% (when taking a dose of 160 mg per day).3 hours after taking the drug, the concentration of telmisartan in the blood plasma is leveled, regardless of the time of food intake.

Distribution

Telmisartan is characterized by a high degree of binding to plasma proteins (> 99.5%), mainly to albumin and alpha>₁-acid glycoprotein. The average apparent volume of distribution at steady state (Vdss) is approximately 500 liters.

Biotransformation

The metabolism of telmisartan consists in conjugation of the parent compound with glucuronic acid. The resulting conjugate has no pharmacological activity.

The elimination

_half-life is more than 20 hours. With_maxand to a lesser extent AUC, they increase disproportionately to the dose increase. There are no data on clinically significant accumulation of telmisartan taken at the recommended doses. It is excreted through the intestines in unchanged form, excretion by the kidneys – less than 2%. Total plasma clearance is high (about 1000 ml / min) compared to “hepatic” blood flow (about 1500 ml / min).

Linearity / non-linearity of pharmacokinetics

There was no linear relationship between the dose of the drug and its plasma concentration. With_maxto a lesser extent, AUC increases disproportionately at doses higher than 40 mg per day.

Special patient populations

Gender of patients

There were differences in the concentration of the drug in blood plasma in men and women: the values with_maxand AUC in women were approximately 3 and 2 times higher than in men, respectively.

Elderly patients

The pharmacokinetics of telmisartan did not differ between elderly patients and patients under 65 years of age.

Patients with impaired renal function

In patients with mild, moderate and severe renal impairment, a 2-fold increase in the concentration of telmisartan in blood plasma was observed. However, in patients with renal insufficiency undergoing hemodialysis, plasma concentrations of the drug were lower. Telmisartan is characterized by a high degree of binding to plasma proteins and is not eliminated from the body by hemodialysis. The_half-life did not change in patients with impaired renal function.

Patients with impaired liver function

The results of pharmacokinetic studies showed an increase in the absolute bioavailability of telmisartan to almost 100% in patients with impaired liver function. The_half-life in patients with impaired liver function did not change.

Indications

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

Use during pregnancy and lactation

The use of Telmista ® Npr during pregnancy is contraindicated.

Hydrochlorothiazide

Experience with the use of hydrochlorothiazide during pregnancy, especially in the first trimester, is limited.

Hydrochlorothiazide penetrates the placental barrier. Taking into account the mechanism of pharmacological action of hydrochlorothiazide, it is assumed that its use in the second and third trimesters of pregnancy can disrupt fetoplacental perfusion and cause such changes in the embryo and fetus as jaundice, impaired water-electrolyte balance and thrombocytopenia.

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

Hydrochlorothiazide should not be used for the treatment of essential hypertension in pregnant women, except in rare situations when other types of treatment cannot be used.

Telmisartan

The use of ARA II in the first trimester of pregnancy is not recommended, 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 prescribed.

The use of ARA II in the second and third trimesters of pregnancy is contraindicated. In preclinical studies on the use of telmisartan, no teratogenic effect was noted, but fetotoxicity was established. It is known that exposure to ARA II in the second and third trimesters of pregnancy causes fetotoxicity in humans (decreased renal function, oligohydramnios, slowing of ossification of the skull bones), as well as neonatal toxicity (renal failure, hypotension, hyperkalemia). Patients planning pregnancy should be prescribed alternative therapy with a proven safety profile for use in pregnant women. If treatment for ARA II occurred in the second trimester of pregnancy, ultrasound examination of the fetal kidneys and skull bones is recommended.

Newborns whose mothers received ARA II should be carefully monitored for hypotension.

Telmista® H therapy is contraindicated during breastfeeding.

In animal studies, the effects of telmisartan and hydrochlorothiazide on fertility were not observed.

Studies on the effect on human fertility have not been conducted.

Contraindications

·  Hypersensitivity to active substances, or auxiliary components of the drug, or other sulfonamide derivatives.

* Pregnancy.

* Breast-feeding period.

* Obstructive diseases of the biliary tract.

·  Severe hepatic impairment (Child-Pugh class C).

·  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 to severe renal impairment (glomerular filtration rate [GFR] less than 60 ml / min/1.73 m2 of body surface area).

* Concomitant use with ACE inhibitors in patients with diabetic nephropathy.

· Fructose or lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome, because Telmista® H contains lactose and sorbitol.

* Children under 18 years of age (efficacy and safety have not been established).

Interaction

Hydrochlorothiazide

Not recommended drug combinations

Lithium preparations

Concomitant use of hydrochlorothiazide and lithium preparations decreases the renal clearance of lithium, which can lead to an increase in the concentration of lithium in blood plasma and increase its toxicity. If concomitant use of hydrochlorothiazide is necessary, the dose of lithium preparations should be carefully selected, the concentration of lithium in blood plasma should be regularly monitored, and the dose of the drug should be adjusted accordingly.

Drug combinations that require special attention

Drugs that can cause polymorphic ventricular tachycardia of the “pirouette”type

Special caution should be exercised when using hydrochlorothiazide concomitantly with medications such as::

• Class I antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide, procainamide) and Class IC antiarrhythmic drugs (flecainide);
• Class III antiarrhythmic drugs (dofetilide, ibutilide, bretilia tosylate), sotalol, dronedarone, amiodarone;
• other (non-antiarrhythmic) drugs, such as:

– antipsychotics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamide (amisulpride, sultopride, sulpiride, tiapride), butyrophenones (droperidol, haloperidol), pimozide, sertindole;

– antidepressants: tricyclic antidepressants, selective inhibitors of serotonin reuptake (SSRIs) (citalopram, ESCITALOPRAM);

– antibacterial agents: fluoroquinolones (levofloxacin, moxifloxacin, sparfloxacin, ciprofloxacin), macrolides (erythromycin intravenous use, azithromycin, clarithromycin, and roxithromycin, spiramycin), co-trimoxazole;

– antifungal agents: the azoles (voriconazole, Itraconazole, ketoconazole, fluconazole);

– anti-malarial drugs (quinine, chloroquine, mefloquine, halofantrine, lumefantrine);

– Antiprotozoal drugs (pentamidine for parenteral use);

– anti-anginal agents (ranolazine, bepridil);

– antineoplastic agents (vandetanib, arsenic trioxide, oxaliplatin, tacrolimus);

– antiemetics (domperidone, ondansetron);

– means of influencing the motility of the gastrointestinal tract (cisapride);

– antihistamines (astemizole, terfenadine, mizolastine);

– other drug (anagrelide, vasopressin, has diphemanil metilsulfate, ketanserin, probucol, propofol, sevoflurane, terlipressin, terodiline, Cilostazol).

Due to the increased risk of ventricular arrhythmias, especially polymorphic ventricular tachycardia of the “pirouette” type (risk factor – hypokalemia), the potassium content in the blood plasma should be determined and, if necessary, adjusted before starting combination therapy with hydrochlorothiazide with the above drugs. It is necessary to monitor the patient’s clinical condition, blood plasma electrolyte content, and ECG parameters. In patients with hypokalemia, it is necessary to use drugs that do not cause polymorphic ventricular tachycardia of the “pirouette”type.

Medicationsthat can increase the duration of the QT interval

Concomitant use of hydrochlorothiazide with medicinal products capable of prolonging the QT interval should be based on a careful assessment of the ratio of expected benefit and potential risk for each patient (there may be an increased risk of developing polymorphic ventricular tachycardia of the “pirouette” type). When using such combinations, it is necessary to regularly record an ECG (to detect prolongation of the QT interval), as well as monitor the content of potassium in the blood plasma.

Drugs that can cause hypokalemia: amphotericin B (with intravenous use), gluco-and mineralocorticosteroids (with systemic use), tetracosactide (adrenocorticotropic hormone [ACTH]), glycyrrhizic acid (carbenoxolone, licorice root preparations), laxativesthat stimulate intestinal motility

Increased risk of hypokalemia when co-administered with hydrochlorothiazide (additive effect). It is necessary to regularly monitor the content of potassium in the blood plasma, if necessary – its correction. Against the background of hydrochlorothiazide therapy, it is recommended to use laxatives that do not stimulate intestinal motility.

Cardiac Glycosides

Hypokalemia and hypomagnesemia due to the action of thiazide diuretics increase the toxicity of cardiac glycosides. With simultaneous use of hydrochlorothiazide and cardiac glycosides, the potassium content in the blood plasma, ECG indicators should be regularly monitored and, if necessary, therapy should be adjusted.

Drug combinationsthat require attention

Other antihypertensive drugs

Potentiation of the antihypertensive effect of hydrochlorothiazide (additive effect). It may be necessary to adjust the dose of simultaneously prescribed antihypertensive drugs.

Ethanol, barbiturates, antipsychotics (neuroleptics), antidepressants, anxiolytics, narcotic analgesics, and general anaesthetics

It is possible to increase the antihypertensive effect of hydrochlorothiazide and potentiate orthostatic hypotension (additive effect).

Non-depolarizing muscle relaxants (e. g. tubocurarine)

It is possible to increase the effect of non-depolarizing muscle relaxants.

Adrenomimetics (pressor amines)

Hydrochlorothiazide may reduce the effect of adrenomimetics such as epinephrine (epinephrine) and norepinephrine (norepinephrine).

Nonsteroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 (COX–2) inhibitors and high doses of acetylsalicylic acid (≥3 g / day)

NSAIDs may reduce the diuretic and antihypertensive effects of hydrochlorothiazide. With simultaneous use, there is a risk of developing acute renal failure due to a decrease in GFR. Hydrochlorothiazide may increase the toxic effects of high-dose salicylates on the central nervous system.

Hypoglycemic agents for oral use and insulin

Thiazide diuretics affect glucose tolerance (hyperglycemia may develop) and reduce the effectiveness of hypoglycemic agents (dose adjustment of hypoglycemic agents may be required).

Caution should be exercised when concomitantly using hydrochlorothiazide and metformin due to the risk of lactic acidosis due to impaired renal function caused by hydrochlorothiazide.

Beta-blockers, diazoxide

Concomitant use of thiazide diuretics (including hydrochlorothiazide) with beta-blockers or diazoxide may increase the risk of hyperglycemia.

Medications used to treat gout (probenecid, sulfinpyrazone, allopurinol)

It may be necessary to adjust the dose of uricosuric drugs, since hydrochlorothiazide increases the concentration of uric acid in the blood serum. Thiazide diuretics may increase the frequency of hypersensitivity reactions to allopurinol.

Amantadine

Thiazide diuretics (including hydrochlorothiazide) may reduce the clearance of amantadine, lead to an increase in the concentration of amantadine in blood plasma, and increase the risk of its undesirable effects.

Anticholinergic drugs (cholinoblockers)

Anticholinergic drugs (for example, atropine, biperiden) increase the bioavailability of thiazide diuretics by reducing gastrointestinal motility and gastric emptying rate.

Cytotoxic (antitumor) drugs

Thiazide diuretics reduce the renal excretion of cytotoxic drugs (for example, cyclophosphamide and methotrexate) and potentiate their myelosuppressive effect.

Methyldopa

Cases of hemolytic anemia with simultaneous use of hydrochlorothiazide and methyldopa are described

Antiepileptic drugs (carbamazepine, oxcarbazepine, topiramate)

Risk of developing symptomatic hyponatremia. With simultaneous use of hydrochlorothiazide and carbamazepine, it is necessary to monitor the patient’s condition and monitor the sodium content in the blood serum. With simultaneous use of hydrochlorothiazide and topiramate, the content of topiramate in the blood serum should also be monitored, if necessary, potassium preparations should be prescribed or the dose of topiramate should be adjusted.

SSRIs

When used concomitantly with thiazide diuretics, hyponatremia may be potentiated. It is necessary to monitor the sodium content in the blood plasma.

Cyclosporine

Concomitant use of thiazide diuretics and cyclosporine increases the risk of hyperuricemia and gout exacerbation.

Oral anticoagulants

Thiazide diuretics may reduce the effect of oral anticoagulants.

Iodine-containing contrast agents

Dehydration of the body while taking thiazide diuretics increases the risk of acute renal failure, especially when using high doses of iodine-containing contrast agents. Before applying iodine-containing contrast agents, it is necessary to compensate for the loss of fluid.

Calcium supplements

With simultaneous use, it is possible to increase the content of calcium in the blood plasma and develop hypercalcemia due to a decrease in the excretion of calcium ions by the kidneys. If simultaneous use of calcium-containing drugs is necessary, then the content of calcium in the blood plasma should be monitored and the dose of calcium preparations adjusted.

Anionic exchange resins (colestyramine and colestipol)

Anionic exchange resins reduce the absorption of hydrochlorothiazide. Single doses of colestyramine and colestipol reduce the absorption of hydrochlorothiazide in the gastrointestinal tract by 85% and 43%, respectively.

Telmisartan

Concomitant use of telmisartan with

· * other antihypertensive agents may increase the antihypertensive effect. In one study, the combined use of telmisartan and ramipril_{resulted in a 2.5-fold increase in plasma AUC of 0-24 and CMAX} of ramipril and ramiprilate. The clinical significance of this interaction has not been established.

When analyzing the adverse events that led to discontinuation of treatment, and analyzing the serious adverse events obtained during the clinical study, it was found that cough and angioedema were more often observed against the background of ramipril therapy, while arterial hypotension was more common against the background of telmisartan therapy. Cases of hyperkalemia, renal failure, hypotension and syncope were observed significantly more frequently with the simultaneous use of telmisartan and ramipril·

* lithium preparations showed a reversible increase in the content of lithium in blood plasma, accompanied by toxic phenomena when taking ACE inhibitors. In rare cases, such changes have been reported with the appointment of ARA II, in particular, telmisartan. When lithium and ARA II preparations are used concomitantly, it is recommended to determine the lithium content in blood plasma·

* NSAIDs, including acetylsalicylic acid in doses used as an anti-inflammatory agent, cyclooxygenase-2 (COX-2) inhibitors and non-selective NSAIDs, may cause acute renal failure in patients with reduced BCC. Drugs that affect the renin-angiotensin-aldosterone system (RAAS) may have a synergistic effect. In patients taking concomitant NSAIDs and telmisartan, BCC should be compensated and renal function monitored at the beginning of treatment.

A reduction in the effect of antihypertensive agents, such as telmisartan, by inhibiting the vasodilating effect of prostaglandins has been observed with concomitant treatment with NSAIDs. No clinically significant effect was observed when telmisartan was co-administered with ibuprofen or paracetamol·

* digoxin, warfarin, hydrochlorothiazide, glibenclamide, simvastatin and amlodipine did not have a clinically significant interaction. There was an increase in the average concentration of digoxin in blood plasma by an average of 20% (in one case by 39%). With simultaneous use of telmisartan and digoxin it is advisable to periodically determine the concentration of digoxin in plasma;

· aliskiren, iliskilendirmesi drugs clinical data has shown that dual blockade of RAAS through the simultaneous use of ACE inhibitors, ARA II and aliskiren is associated with a high incidence of adverse effects such as hypotension, hyperkalemia, decreased renal function (including acute renal failure) compared to the use of a single RAAS activity blocker. Concomitant use of ARA II with drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or moderate or severe renal insufficiency (GFR less than 60 ml/min / 1.73 m%^%2 of body surface area) and is not recommended in other patients. Concomitant use of ARA IIcwith ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients·

* drugs that can cause hyperkalemia

Like other drugs that act on the RAAS, telmisartan may increase the risk of hyperkalemia. The risk may be increased in case of simultaneous use with other drugs that can cause hyperkalemia (salt substitutes containing potassium, potassium-sparing diuretics [spironolactone, eplerenone, triamterene or amiloride], ACE inhibitors, ARA II and NSAIDs, including selective COX-2 inhibitors, heparin, immunosuppressants [cyclosporine, tacrolimus and trimethoprim]). Caution should be exercised when using it concomitantly and periodically monitor the level of potassium in the blood plasma·

* diuretics (thiazide or “loop”)

Previous treatment with high doses of diuretics, such as furosemide (loop diuretic) and hydrochlorothiazide (thiazide diuretic), may lead to hypovolemia and the risk of hypotension at the beginning of telmisartan treatment·

* corticosteroids (for systemic use)

Corticosteroids weaken the antihypertensive effect of telmisartan.

How to take, course of use and dosage

Inside, regardless of the meal time.

Telmista® should be taken once a day.

· Drug Temesta® NV dose hydrochlorothiazide 12.5 mg + telmisartan 40 mg can be administered to patients in whom the use of telmisartan at a dose of 40 mg or hydrochlorothiazide does not lead to adequate control of blood pressure.

· The drug Temesta® NV dose hydrochlorothiazide 12.5 mg + telmisartan 80 mg can be administered to patients in whom the use of telmisartan at a dose of 80 mg or drug Temesta® NV dose hydrochlorothiazide 12.5 mg + telmisartan 40 mg does not lead to adequate control of blood pressure.

· The drug Temesta®NV dose of hydrochlorothiazide 25 mg + telmisartan 80 mg can be administered to patients in whom the use of telmisartan at a dose of 80 mg or drug Temesta® NV dose hydrochlorothiazide 12.5 mg + telmisartan 80 mg does not lead to adequate control of blood pressure, or patients previously stabilized telmisartan or hydrochlorothiazide when applied separately.

In patients with severe hypertension, the maximum daily dose of telmisartan 160 mg in monotherapy or in combination with hydrochlorothiazide 12.5-25.0 mg is effective and well tolerated.

Impaired renal function

Limited experience with the hydrochlorothiazide combination + telmisartan in patients with mild or moderate renal impairment does not require a change in the dose of the drug in these cases. In such patients, renal function should be monitored (see section “Contraindications” for use with creatinine clearance less than 30 ml/min).

Liver function disorders

In patients with mild to moderate hepatic impairment (Child-Pugh Class A and B), the daily dose of Telmista®is recommended. Do not exceed the dose of hydrochlorothiazide 12.5 mg and telmisartan 40 mg per day (see section ” Pharmacological properties. Pharmacokinetics”).

Elderly patients

The dosage regimen does not require any changes.

Overdose

Information about overdose is limited.

Hydrochlorothiazide

Symptoms

The most common manifestations of hydrochlorothiazide overdose are increased diuresis, accompanied by acute fluid loss (dehydration) and electrolyte disturbances (hypokalemia, hyponatremia, hypochloremia). Overdose with hydrochlorothiazide can manifest the following symptoms::

• from the side of cardiovascular system: tachycardia, decreased blood pressure, shock;
• from the nervous system: weakness, confusion, dizziness, and cramps of the calf muscles, paresthesia, impaired consciousness, fatigue;
• the gastro-intestinal tract: nausea, vomiting, thirst;
• the part of the kidney and urinary tract disorders: polyuria, oliguria or anuria (due to hemoconcentration);
• laboratory findings: hypokalemia, hyponatremia, gipohloremia, alkalosis, increased concentration of residual nitrogen urea in blood plasma (particularly in patients with renal insufficiency).

Treatment

In case of overdose, symptomatic and supportive therapy is performed. If hydrochlorothiazide has been taken recently, induction of vomiting or gastric lavage is indicated for its elimination. Absorption of hydrochlorothiazide can be reduced by ingestion of activated carbon. In case of a decrease in blood pressure or shock, BCC should be replenished with the introduction of plasma-substituting fluids and electrolyte deficiency (potassium, sodium). In case of respiratory failure, oxygen inhalation or artificial ventilation is indicated. It is necessary to monitor the water-electrolyte balance (especially the potassium content in the blood serum) and kidney function before their normalization.

There is no specific antidote. Hydrochlorothiazide is eliminated by hemodialysis, but the degree of its elimination has not been established.

Telmisartan

Symptoms

The most pronounced signs of overdose were excessive lowering of blood pressure and tachycardia, and bradycardia, dizziness, increased serum creatinine, and acute renal failure were also reported.

Treatment

Telmisartan is not eliminated by hemodialysis. Patients ‘ condition should be carefully 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 provoking vomiting and / or gastric lavage, and taking activated charcoal is advisable. Electrolyte levels and plasma creatinine levels should be monitored regularly. If there is a marked decrease in blood pressure, the patient should take a horizontal position with raised legs, while it is necessary to quickly replenish the volume of BCC and the content of electrolytes.

Description

Tablets 12.5 mg + 40 mg:

Oval, biconvex, two-layer tablets, one layer from white to almost white or pinkish-white, the other layer is pink with inclusions of light pink and dark pink.

Tablets 12.5 mg + 80 mg:

Oval, biconvex, two-layer tablets, one layer from white to almost white or pinkish-white, the other layer is pink with inclusions of light pink and dark pink.

Tablets 25 mg + 80 mg:

Oval, biconvex, two-layer tablets, one layer from white to yellowish-white, the other layer is yellow with inclusions of light yellow and dark yellow.

Special instructions

* Bilateral renal artery stenosis or stenosis of the artery of a single kidney (see the section “Special instructions”).

* Impaired liver function or progressive liver disease (Child-Pugh class A and B) (see section “Special Instructions”).

·  Reduced BCC due to previous diuretic therapy, restriction of salt intake, diarrhea or vomiting.

* Hyperkalemia.

* Condition after kidney transplantation (no experience of use).

* Chronic heart failure of functional class III-IV (FC) according to the classification of the New York Heart Association (NYHA).

* Hypercalcemia.

* Hypercholesterolemia.

* Hypertriglyceridemia.

* Hypokalemia.

* Hyponatremia.

· Concomitant use of drugs that can cause polymorphic ventricular tachycardia of the “pirouette” type or increase the duration of the QT interval on the ECG

· * Concomitant use of lithium preparations, drugs that can cause hypokalemia, cardiac glycosides.

* Hyperparathyroidism.

·  Advanced age.

* Coronary heart disease (CHD).

* Progressive liver disease (risk of developing hepatic coma).

* Aortic and/or mitral valve stenosis.

Idiopathic hypertrophic subaortic stenosis.

· Hypertrophic obstructive cardiomyopathy (HOCMP).

· Diabetes mellitus.

* Primary hyperaldosteronism.

·  Gout, hyperuricemia.

* Systemic lupus erythematosus.

* A history of allergic reaction to penicillin.

· A history of non-melanoma skin cancer (NSCLC) (see section “Special instructions”).

·  Use in patients of the black race.

* Experience with use in patients with renal insufficiency (creatinine clearance greater than 30 ml/min) is limited, but does not confirm the development of side effects from the kidneys, and no dose adjustment is required.

It is contraindicated in persons under 18 years of age, as efficacy and safety have not been established.

Impaired renal function

Limited experience with the hydrochlorothiazide combination + telmisartan in patients with mild or moderate renal impairment does not require a change in the dose of the drug in these cases. In such patients, renal function should be monitored (see section “Contraindications” for use with creatinine clearance less than 30 ml/min).

Liver function disorders

In patients with mild to moderate hepatic impairment (Child-Pugh Class A and B), the daily dose of Telmista®is recommended. Do not exceed the dose of hydrochlorothiazide 12.5 mg and telmisartan 40 mg per day (see section ” Pharmacological properties. Pharmacokinetics”).

Elderly patients

The dosage regimen does not require any changes.

Use of Telmista® H is not recommended in patients with acute myocardial infarction due to insufficient clinical experience.

The medicinal product Telmista® H should not be used to relieve a hypertensive crisis.

Hydrochlorothiazide

Impaired renal function

In patients with impaired renal function, hydrochlorothiazide may cause azotemia. In case of renal failure, accumulation of hydrochlorothiazide is possible.

In patients with reduced renal function, periodic monitoring of creatinine clearance is necessary. If renal impairment progresses and / or oliguria (anuria) occurs, hydrochlorothiazide should be discontinued.

Liver function disorders

When using thiazide diuretics in patients with impaired liver function, hepatic encephalopathy may develop. In patients with severe hepatic insufficiency or hepatic encephalopathy, the use of thiazides is contraindicated. In patients with mild to moderate hepatic insufficiency and/or progressive liver disease, hydrochlorothiazide should be used with caution, since even a small change in the water-electrolyte balance and accumulation of ammonium in the blood serum can cause hepatic coma. If symptoms of encephalopathy occur, diuretics should be discontinued immediately.

Water-electrolyte balance and metabolic disorders

Thiazide diuretics (including hydrochlorothiazide) can cause a decrease in BCC (hypovolemia) and disturbances in the water-electrolyte balance (including hypokalemia, hyponatremia, hypochloremic alkalosis).

Clinical symptoms of water-electrolyte balance disorders include dryness of the oral mucosa, thirst, weakness, lethargy, fatigue, drowsiness, restlessness, muscle pain or cramps, muscle weakness, marked decrease in blood pressure, oliguria, tachycardia, arrhythmia, and gastrointestinal disorders (such as nausea and vomiting). In patients receiving hydrochlorothiazide therapy (especially with prolonged treatment), clinical symptoms of water-electrolyte balance disorders should be identified, and the content of electrolytes in blood plasma should be regularly monitored.

Sodium

All diuretics can cause hyponatremia, sometimes leading to severe complications. Hyponatremia and hypovolemia can lead to dehydration and orthostatic hypotension. Concomitant reduction of the chlorine content in blood plasma can lead to secondary compensatory metabolic alkalosis, but the frequency and severity of this effect are insignificant. It is recommended to determine the sodium content in the blood plasma before starting treatment and regularly monitor this indicator against the background of taking hydrochlorothiazide.

Potassium

When using thiazide and thiazide-like diuretics, there is a risk of a sharp decrease in the potassium content in the blood plasma and the development of hypokalemia (the potassium content in the blood plasma is less than 3.4 mmol/l). Hypokalemia increases the risk of developing cardiac arrhythmias (including severe arrhythmias) and increases the toxic effect of cardiac glycosides. In addition, hypokalemia (as well as bradycardia) is a condition that contributes to the development of polymorphic ventricular tachycardia of the “pirouette” type, which can lead to death.

Hypokalemia is most dangerous for the following groups of patients: elderly people, patients receiving simultaneous therapy with antiarrhythmic and non-antiarrhythmic drugs that can cause polymorphic ventricular tachycardia of the “pirouette” type or increase the duration of the QT interval on the ECG, patients with impaired liver function, CHD, CHF. In addition, patients with an extended QT interval are at increased risk. It does not matter whether this increase is caused by congenital causes or the action of medications.

In all the cases described above, it is necessary to avoid the risk of hypokalemia and regularly monitor the potassium content in the blood plasma. The first determination of the potassium content in the blood plasma should be carried out within the first week after the start of treatment. If hypokalemia occurs, appropriate treatment should be prescribed. Hypokalemia can be corrected by using potassium-containing medications or by taking foods rich in potassium (dried fruits, fruits, vegetables).

Calcium

Thiazide diuretics can reduce the excretion of calcium ions by the kidneys, leading to a slight and temporary increase in the content of calcium in the blood plasma. In some patients with prolonged use of thiazide diuretics, pathological changes in the parathyroid glands with hypercalcemia and hyperphosphatemia were observed, but without the typical complications of hyperparathyroidism (nephrolithiasis, decreased bone mineral density, peptic ulcer disease). Severe hypercalcemia may be a manifestation of previously undiagnosed hyperparathyroidism.

Because of their effect on calcium metabolism, thiazides can affect laboratory parameters of parathyroid function. Thiazide diuretics (including hydrochlorothiazide) should be discontinued prior to parathyroid function testing.

Magnesium

Thiazides have been found to increase the excretion of magnesium ions by the kidneys, which can lead to hypomagnesemia. The clinical significance of hypomagnesemia remains unclear.

Glucose

Treatment with thiazide diuretics may impair glucose tolerance. When using hydrochlorothiazide in patients with manifest or latent diabetes mellitus, it is necessary to regularly monitor the concentration of glucose in the blood. Dose adjustment of hypoglycemic medications may be required.

Uric acid

In patients with gout, the frequency of seizures may increase or the course of gout may worsen. Patients with gout and impaired uric acid metabolism (hyperuricemia) should be carefully monitored.

Lipids

When using hydrochlorothiazide, the concentration of cholesterol and triglycerides in the blood plasma may increase.

Acute myopia / secondary angle-closure glaucoma

Hydrochlorothiazide can cause an idiosyncratic reaction, leading to the development of acute myopia and an acute attack of secondary angle-closure glaucoma. Symptoms include: a sudden decrease in visual acuity or pain in the eyes, which usually manifests itself within a few hours or weeks from the start of hydrochlorothiazide therapy. If left untreated, acute angle-closure glaucoma can lead to permanent vision loss. If symptoms occur, stop taking hydrochlorothiazide as soon as possible. If intraocular pressure remains uncontrolled, urgent medical treatment or surgery may be required. Risk factors for acute angle-closure glaucoma include: a history of allergic reaction to sulfonamides or penicillin.

Immune system disorders

There are reports that thiazide diuretics (including hydrochlorothiazide) can cause exacerbation or progression of systemic lupus erythematosus, as well as lupus-like reactions.

Hypersensitivity reactions may occur in patients receiving thiazide diuretics even if there is no indication of a history of allergic reactions or bronchial asthma.

Photosensitivity

There is information about cases of photosensitivity reactions when taking thiazide diuretics. If photosensitivity occurs while taking hydrochlorothiazide, treatment should be discontinued. If continued use of the diuretic is necessary, then the skin should be protected from exposure to sunlight or artificial ultraviolet (UV) rays.

NMRC

Two pharmacoepidemiological studies using data from the Danish National Cancer Registry demonstrated an association between hydrochlorothiazide intake and an increased risk of NSCLC-basal cell carcinoma and squamous cell carcinoma. The risk of developing NSCLC increased with an increase in the total (accumulated) dose of hydrochlorothiazide. A possible mechanism for the development of NSCLC is the photosensitizing effect of hydrochlorothiazide.

Patients taking hydrochlorothiazide alone or in combination with other medications should be aware of the risk of developing NSCLC. Such patients are advised to have their skin examined regularly to identify any new suspicious lesions, as well as changes to existing skin lesions.

All suspicious skin changes should be reported to your doctor immediately. Suspicious skin areas should be examined by a specialist. To clarify the diagnosis, histological examination of skin biopsies may be required.

In order to minimize the risk of developing NSCLC, patients should be advised to take preventive measures, such as limiting exposure to sunlight and UV rays, as well as using appropriate protective equipment.

In patients with a history of NSCLC, it is recommended to reconsider the use of hydrochlorothiazide.

Alcohol

During the treatment period, it is not recommended to consume alcoholic beverages, becauseethanol enhances the antihypertensive effect of thiazide diuretics.

Athletes

Hydrochlorothiazide can give a positive result during doping control in athletes.

Other things

In patients with severe atherosclerosis of the cerebral and coronary arteries, hydrochlorothiazide should be used with extreme caution.

Thiazide diuretics can reduce the amount of iodine bound to plasma proteins without showing signs of thyroid dysfunction.

Telmisartan

Liver failure

Telmisartan should not be used in patients with cholestasis, biliary tract obstruction, or severe hepatic impairment (Child-Pugh Class C). since telmisartan is mainly excreted in the bile. It is assumed that the hepatic clearance of telmisartan is reduced in such patients.

Renovascular hypertension

Patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney are at increased risk of severe hypotension and renal failure when treated with drugs acting on the RAAS.

Double blockade of the RAAS

Data on the concomitant use of ACE inhibitors with ARA II or sprays containing aliskiren confirm an increased risk of a sharp decrease in blood pressure, the development of hyperkalemia and impaired renal function (including acute renal failure).

Concomitant use of ARA II, including telmisartan, with drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or moderate to severe renal insufficiency (GFR less than 60 ml/min / 1.73 m2 of body surface area) and is not recommended in other patients.

Concomitant use of ARA II, including telmisartan, with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

If it is necessary to carry out a double blockade of the RAAS, each case should be considered individually and renal function, water-electrolyte balance and blood pressure indicators should be carefully monitored.

Other diseases characterized by RAAS stimulation

In patients whose vascular tone and renal function depend primarily on RAAS activity (for example, patients with CHF or kidney disease, including renal artery stenosis), the use of drugs acting on this system, such as telmisartan, has been associated with the occurrence of acute arterial hypotension, hyperazotemia, oliguria, or rarely with acute renal failure.

Primary hyperaldosteronism

Patients with primary hyperaldosteronism generally do not respond to treatment with antihypertensive drugs that inhibit RAAS. In this regard, the use of telmisartan in these cases is not recommended.

Kidney failure and kidney transplantation

There is no clinical experience with the use of telmisartan in patients who have recently undergone kidney transplantation.

BCC reduction

Patients with reduced BCC and/or plasma sodium levels due to previous diuretic therapy, salt restriction, diarrhea, or vomiting may experience symptomatic hypotension, especially after the first dose of telmisartan.

Aortic and mitral valve stenosis, HOCMP

As with other vasodilators, caution should be exercised when prescribing the drug to patients with aortic, mitral valve stenosis or HOCMP.

Hyperkalemia

Telmisartan may lead to hyperkalemia due to angiotensin II receptor antagonism (AT1 subtype). For elderly patients, patients with renal insufficiency, patients with diabetes mellitus and also with arterial hypertension and CHD, patients receiving concomitant therapy with drugs that can cause an increase in potassium content, and/or patients with concomitant diseases, hyperkalemia can lead to a fatal outcome. Before considering the possibility of concomitant use of drugs acting on the RAAS, it is necessary to assess the benefit-risk ratio. The main risk factors to consider are::

· diabetes mellitus, renal failure, heart failure, elderly age (patients over 70 years of age);

* combination with one or more drugs acting on the RAAS and/or dietary supplements containing potassium. Drugs that can cause hyperkalemia, are potassium-sparing diuretics, ACE inhibitors, ARA II, NSAIDs, including selective COX-2 inhibitors, heparin, immunosuppressants (cyclosporine or tacrolimus), trimethoprim, as well as salt substitutes containing potassium;

· related disease or condition, in particular dehydration, acute cardiac decompensation, metabolic acidosis, impaired renal function, acute renal failure (e. g., infectious diseases), the cytolysis syndrome (e. g. acute limb ischemia, rhabdomyolysis, extensive trauma).

Form of production

Tablets,12.5 mg +40 mg,12.5 mg + 80 mg,25 mg + 80 mg.

7 or 10 tablets in a blister made of a combined OPA/Al / PVC material-aluminum foil.

2,4,8,12 or 14 blisters of 7 tablets or 3,6,9 or 10 blisters of 10 tablets are placed in a cardboard pack together with the instructions for use.

Storage conditions

Storage conditions

At a temperature not exceeding 25 °C, in the original packaging (blister pack).

Keep out of reach of children.

Shelf

life is 2 years.

Do not use the drug after the expiration date.

Active ingredient

Telmisartan, Hydrochlorothiazide

Conditions of release from pharmacies

By prescription

Dosage form

Tablets