Telmista N, tablets 12.5mg+80 mg 84 pcs

hypotensive agent combined (diuretic + angiotensin II receptor antagonist)

Indications

Arterial hypertension (if telmisartan or hydrochlorothiazide are ineffective in monotherapy).

Active ingredient

Composition

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

Active substances:

Hydrochlorothiazide 12.50 mg/12.50 mg/25.00 mg

Telmisartan 40.00 mg/80.00 mg/80.00 mg

Supplementary substances:

Meglumine, sodium hydroxide, povidone-K30, lactose monohydrate, sorbitol, magnesium stearate, mannitol, mannitol DC, iron oxide yellow dye (E172) (for 25 mg + 80 mg tablets), Ferric oxide red dye (E172) (for tablets 12.5 mg + 40 mg and 12.5 mg + 80 mg), hyprolose, colloidal silicon dioxide, sodium stearyl fumarate/p>

How to take, the dosage

Orally, regardless of the time of meals.

The drug Telmista® Needs to be taken once daily.

– Telmista® H in a dose of 12.5 mg hydrochlorothiazide + telmisartan 40 mg can be administered to patients in whom telmisartan 40 mg or hydrochlorothiazide does not adequately control BP.

– The drug Telmista® H at a dose of 12.5 mg hydrochlorothiazide + 80 mg telmisartan may be administered to patients in whom the use of 80 mg telmisartan or the drug Telmista® H at a dose of hydrochlorothiazide 12.5 mg + telmisartan 40 mg does not adequately control BP.

– The drug Telmista®N at a dose of 25 mg hydrochlorothiazide + 80 mg telmisartan may be administered to patients in whom the use of 80 mg telmisartan or the drug Telmista® H at a dose of 12.5 mg hydrochlorothiazide + telmisartan 80 mg does not adequately control BP, or patients whose condition has previously been stabilized by telmisartan or hydrochlorothiazide when administered separately.

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

Kidney function disorders

Limited experience with the combination of hydrochlorothiazide + telmisartan in patients with mild to moderately severe renal impairment does not warrant a change in the dose of the drug in these cases. In these patients renal function should be monitored (for use at CKR less than 30 ml/min see section “Contraindications”).

Liver function disorders

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

Elderly patients

No dosing regimen changes required.

Interaction

Hydrochlorothiazide

Unrecommended drug combinations

Lithium drugs

Simultaneous use of hydrochlorothiazide and lithium drugs decreases renal clearance of lithium, which may increase the concentration of lithium in blood plasma and increase its toxicity. If it is necessary to use hydrochlorothiazide concomitantly, the dose of lithium preparations should be chosen carefully, the lithium concentration in blood plasma should be controlled regularly, and the dose of the drug should be adjusted accordingly.

Drug combinations requiring special attention

Drugs that can cause pirouette-type polymorphic ventricular tachycardia

Hydrochlorothiazide should be used with extreme caution simultaneously with drugs such as:

– neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpiride, thiapride), butyrophenones (droperidol, haloperidol), pimozide, sertindol;

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

– antibacterial agents: Fluoroquinolones (levofloxacin, moxifloxacin, sparfloxacin, ciprofloxacin), macrolides (erythromycin when given intravenously, azithromycin, clarithromycin, roxithromycin, spiramycin), co-trimoxazole;

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

– antimalarials (quinine, chloroquine, mefloquine, halofantrine, lumefantrine);

– antiprotozoal agents (pentamidine in parenteral administration);

– antianginal agents (ranolazine, bepridil);

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

– antiemetics (domperidone, ondansetron);

– agents affecting gastrointestinal motility (cisapride);

– antihistamines (astemizole, terfenadine, misolastine);

– other drugs (anagrelide, vasopressin, difemanil methylsulfate, ketanserin, probucol, propofol, sevoflurane, terlipressin, terdilin, cilostazol).

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

Drugs that can prolong the interval length QT

The concomitant use of hydrochlorothiazide with drugs capable of prolonging QT interval should be based on a careful evaluation for each patient of the ratio of expected benefit to potential risk (an increased risk of polymorphic ventricular pirouette tachycardia may occur). While using such combinations it is necessary to record ECG regularly (for detection of prolongation of QT interval) as well as to monitor potassium content in blood plasma.

Drugs that can cause hypokalemia: Amphotericin B (when administered intravenously), gluco- and mineralocorticosteroids (when administered systemically), tetracosactide (adrenocorticotropic hormone [ACTH]), glycyrrhizic acid (carbenoxolone, preparations containing licorice root), laxatives, stimulating intestinal motility

Increased risk of hypokalemia when concomitantly used with hydrochlorothiazide (additive effect). Regular monitoring of plasma potassium is necessary, and its correction, if necessary. Against the background of hydrochlorothiazide therapy it is recommended to use laxatives which do not stimulate intestinal motility.

Heart glycosides

Hypokalemia and hypomagnesemia due to thiazide diuretics increase the toxicity of cardiac glycosides. When using hydrochlorothiazide and cardiac glycosides concomitantly, plasma potassium and ECG parameters should be monitored regularly and the therapy should be adjusted if necessary.

Drug combinations.drug combinations

Other hypotensive drugs

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

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

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

Nedepolarizing myorelaxants (e.g., tubocurarine)

The effect of nondepolarizing myorelaxants may be enhanced.

Adrenomimetics (pressor amines)

Hydrochlorothiazide may decrease the effect of adrenomimetics such as epinephrine (adrenaline) and norepinephrine (noradrenaline).

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

NSAIDs may decrease the diuretic and antihypertensive effects of hydrochlorothiazide. With concomitant use, there is a risk of acute renal failure due to decreased FFR. Hydrochlorothiazide may increase the toxic effects of high doses of salicylates on the central nervous system.

Hypoglycemic agents for oral administration and insulin

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

We should use hydrochlorothiazide and metformin with caution due to the risk of lactoacidosis due to hydrochlorothiazide-induced renal dysfunction.

Beta-adrenoblockers, diazoxide

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

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

Dose adjustment of uricosuric drugs may be necessary because hydrochlorothiazide increases serum uric acid concentrations. Thiazide diuretics may increase the incidence of hypersensitivity reactions to allopurinol.

Amantadine

Thiazide diuretics (including hydrochlorothiazide) may decrease amantadine clearance, lead to higher plasma amantadine concentrations and increase the risk of adverse effects.

Anticholinergic drugs (choline blockers)

Anticholinergic drugs (e.g., atropine, biperiden) increase the bioavailability of thiazide diuretics by reducing the GI motility and gastric emptying rate.

Cytotoxic (antitumor) drugs

Thiazide diuretics reduce renal excretion of cytotoxic drugs (e.g., cyclophosphamide and methotrexate) and potentiate their myelosuppressive effects.

Methyldopa

Cases of hemolytic anemia have been described when hydrochlorothiazide and methyldopa have been used simultaneously

Antioepileptic drugs (carbamazepine, oxcarbazepine, topiramate)

Risk of developing symptomatic hyponatremia. In concomitant use of hydrochlorothiazide and carbamazepine it is necessary to monitor the patient’s condition and control serum sodium content. When using hydrochlorothiazide and topiramate concomitantly, the content of topiramate in blood serum should also be monitored and if necessary potassium preparations or topiramate dose should be administered.

SOCIATION

When concomitant use with thiazide diuretics, hyponatremia may potentiate. It is necessary to control the sodium content in blood plasma.

Cyclosporine

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

Peroral anticoagulants

Thiazide diuretics may decrease the effect of oral anticoagulants.

Iodine contrast agents

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

Calcium preparations

When concomitant use is possible increase of calcium content in blood plasma and development of hypercalcemia due to decrease of calcium ions excretion by kidneys. If simultaneous use of calcium containing medicines is necessary, the calcium content in plasma should be monitored and the dose of calcium preparations should be corrected.

Anion exchange resins (colestyramine and colestipol)

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

Telmisartan

When telmisartan is used concomitantly with:

– other hypotensive agents may increase antihypertensive effects. In one study, a 2.5-fold increase in plasma AUC0-24 and Cmax of ramipril and ramiprilat was observed when telmisartan and ramipril were combined. The clinical significance of this interaction has not been established.

In an analysis of adverse events leading to treatment discontinuation and an analysis of serious adverse events from the clinical trial, it was found that cough and angioneurotic edema were more frequently observed with ramipril therapy, whereas arterial hypotension was more frequently observed with telmisartan therapy. Cases of hyperkalemia, renal failure, arterial hypotension, and syncope were significantly more frequently observed with concomitant use of telmisartan and ramipril;

– lithium preparations have reported reversible increases in plasma lithium, accompanied by toxic effects with ACE inhibitors. In rare cases, similar changes have been reported when prescribing ARA II, in particular telmisartan. It is recommended to determine lithium content in blood plasma when concomitant use of lithium and ARA II drugs;

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

Decreased effect of hypotensive agents such as telmisartan through inhibition of vasodilatory effect of prostaglandins was noted when simultaneously treated with NSAIDs. No clinically significant effect was observed with concomitant use of telmisartan with ibuprofen or paracetamol;

– digoxin, warfarin, hydrochlorothiazide, glibenclamide, simvastatin and amlodipine showed no clinically significant interaction. There was an increase in the average plasma concentration of digoxin by an average of 20% (in one case by 39%). If telmisartan and digoxin are used concomitantly, periodic determination of plasma concentration of digoxin is reasonable;

– aliskiren, aliskiren-containing drugs .clinical data showed that dual RAAS blockade by concomitant use of ACE inhibitors, ARA II and aliskiren is associated with a high incidence of side effects such as arterial hypotension, hyperkalemia, decreased renal function (including acute renal failure) compared with the use of a single RAAS activity blocker. Concomitant use of APA II with drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or with moderate or severe renal insufficiency (FFR less than 60 ml/min/1.73 m2 body surface area) and is not recommended in other patients. Concomitant use of ARA IIcACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients;

– drugs that can cause hyperkalemia

Like other drugs acting on the RAAS, telmisartan may provoke a risk of hyperkalemia. The risk may be increased in case of concomitant use with other drugs that may cause hyperkalemia (Potassium-containing salt substitutes, potassium-saving diuretics [spironolactone, eplerenone, triamterene or amiloride], ACE inhibitors, ARAs II and NSAIDs including selective COX-2 inhibitors, heparin, immunosuppressants [cyclosporine, tacrolimus and trimethoprim]). Caution should be used concomitantly and plasma potassium levels should be periodically monitored;

– diuretics (thiazide or “loop”)

Previous treatment with high-dose diuretics, such as furosemide (“loop” diuretic) and hydrochlorothiazide (a thiazide diuretic), may lead to hypovolemia and risk of arterial hypotension at the start of telmisartan treatment;

– corticosteroids (for systemic use)

Corticosteroids attenuate the antihypertensive effect of telmisartan.

Special Instructions

– Bilateral renal artery stenosis or single renal artery stenosis (see “Special Instructions”).

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

– Decreased RBC due to prior therapy with diuretics, restriction of table salt, diarrhea, or vomiting.

– Hyperkalemia.

Post kidney transplant condition (no experience of use).

– New York Heart Association (NYHA) class III-IV chronic heart failure.

– Hypercalcemia.

– Hypercholesterolemia.

– Hypertriglyceridemia.

– Hypokalemia.

– Hyponatremia.

– Concomitant use of drugs that may cause pirouette-type polymorphic ventricular tachycardia or prolong QT interval duration on ECG.

Concurrent use of lithium, drugs that may cause hypokalemia, cardiac glycosides.

– Hyperparathyroidism.

– Older age.

– Coronary heart disease (CHD).

– Progressive liver disease (risk of liver coma).

-Aortic and/or mitral valve stenosis.

– Idiopathic hypertrophic subaortic stenosis.

– Hypertrophic obstructive cardiomyopathy (HCMP).

– Diabetes.

– Primary hyperaldosteronism.

– Gout, hyperuricemia.

– Systemic lupus erythematosus.

– A history of allergic reaction to penicillin.

– A history of nonmelanoma skin cancer (NSCLC) (see “Special Indications”).

– Use in patients of Negro race.

– Experience with use in patients with renal impairment (CK greater than 30 ml/min) is limited but does not confirm the development of renal side effects, and no dose adjustment is required.

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

Kidney function disorders

Limited experience with the combination of hydrochlorothiazide + telmisartan in patients with mild to moderately severe renal impairment does not warrant a change in the dose of the drug in these cases. In these patients renal function should be monitored (for use at CKR less than 30 ml/min see section “Contraindications”).

Liver function disorders

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

Elderly patients

The dosing regimen does not require changes.

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

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

Hydrochlorothiazide

Kidney function disorders

In patients with renal function disorders, hydrochlorothiazide may cause azotemia. In patients with renal insufficiency, hydrochlorothiazide may cumulate.

In patients with reduced renal function, periodic CK monitoring is necessary. In progression of renal function impairment and/or onset of oliguria (anuria), hydrochlorothiazide should be discontinued.

Liver function disorders

Hepatic encephalopathy may develop when using thiazide diuretics in patients with hepatic dysfunction. In patients with severe hepatic insufficiency or hepatic encephalopathy thiazide use is contraindicated. In patients with mild to moderate hepatic insufficiency and/or progressive liver disease hydrochlorothiazide should be used with caution, since even a slight change of electrolyte-water balance and accumulation of ammonium in blood serum may cause hepatic coma. In case of encephalopathy symptoms the use of diuretics should be immediately stopped.

Water-electrolyte balance and metabolic disorders

Synopsis

Tablets 12.5 mg + 40 mg:

Oval, biconvex, double-layered tablets, one layer white to almost white or pinkish-white in color, the other layer pink with flecks of light pink and dark pink.

Tablets 12.5 mg + 80 mg:

Oval, biconvex, double-layered tablets, one layer white to almost white or pinkish-white in color, the other layer pink with flecks of light pink and dark pink.

Tablets 25 mg + 80 mg:

Oval, biconvex, double-layered tablets, one layer white to yellowish-white, the other layer yellow with flecks of light yellow and dark yellow.

Contraindications

– Hypersensitivity to the active ingredients or excipients of the drug or other sulfonamide derivatives.

– Pregnancy.

Breast-feeding period.

– Obstructive biliary diseases.

– Severe liver function disorders (Child-Pugh class C).

– Severe renal impairment (CK less than 30 ml/min).

– Refractory hypokalemia, hypercalcemia.

– Concurrent use with aliskiren and drugs containing aliskiren in patients with diabetes and/or with moderate or severe renal function impairment (glomerular filtration rate [GFR] less than 60 ml/min/1.73 m2 body surface area).

– Concurrent use with ACE inhibitors in patients with diabetic nephropathy.

– Fructose or lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome, as. Telmista® contains neither lactose nor sorbitol.

– Children under 18 years (effectiveness and safety not established).

Overdose

Overdose information 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 may manifest as the following symptoms:

Treatment

In case of overdose, symptomatic and supportive therapy is given. If hydrochlorothiazide was taken recently, induction of vomiting or gastric lavage are indicated for its elimination. Absorption of hydrochlorothiazide may be reduced by ingestion of activated charcoal. In case of BP decrease or shock it is necessary to replenish CIC by administration of plasma exchange fluids and electrolyte deficit (potassium, sodium). In case of respiratory failure, oxygen inhalation or artificial lung ventilation is indicated. Water-electrolyte balance (especially, potassium content in blood serum) and kidney function should be controlled until their normalization.

There is no specific antidote. Hydrochlorothiazide is excreted by hemodialysis, but the extent of its excretion has not been established.

Telmisartan

Symptoms

The most prominent manifestations of overdose were excessive BP decrease and tachycardia; bradycardia, dizziness, increased serum creatinine concentration, and acute renal failure were also reported.

Treatment

Telmisartan is not excreted by hemodialysis. Patients should be closely monitored and symptomatic as well as supportive treatment should be implemented. The treatment approach depends on the time since the drug was taken and the severity of the symptoms. Recommended interventions include inducing vomiting and/or gastric lavage, and administration of activated charcoal is advisable. Electrolytes and plasma creatinine concentration should be regularly monitored. If marked BP decrease occurs, the patient should assume horizontal position with elevated legs, and the BCC volume and electrolytes content should be quickly replenished.

Pregnancy use

The use of Telmista® H in pregnancy is contraindicated.

Hydrochlorothiazide

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

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

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

Hydrochlorothiazide should not be used to treat essential hypertension in pregnant women except in those rare situations where other treatments cannot be used.

Telmisartan

The use of ARA II in the first trimester of pregnancy is not recommended; these drugs should not be prescribed in pregnancy. If pregnancy is diagnosed, the drug should be discontinued immediately. If necessary, alternative therapy (other classes of hypotensive drugs approved for use in pregnancy) should be prescribed.

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

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

Telmista® H therapy is contraindicated during breastfeeding.

Telmisartan and hydrochlorothiazide did not affect fertility in animal studies.

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

Similarities