Tarka tablets with modified release p / o 180mg + 2mg, No. 28

Essential arterial hypertension (for patients for whom combination therapy is indicated).

Inside. The capsule is swallowed whole with water.

The drug is best taken in the morning after meals.

The recommended dose for adults is 1 caps. in a day.

active substances: trandolapril - 2 mg

excipients: corn starch; lactose monohydrate; povidone (K25); sodium stearyl fumarate

Film-coated tablet:

verapamil hydrochloride - 180 mg

excipients: MCC; sodium alginate; povidone (K30); magnesium stearate; purified water

film coating: hypromellose 6 mPa; hypromellose 15 mPa; hyprolosis 7 mPa; macrogol 400; macrogol 6000; talc; colloidal silicon dioxide; sodium docusat; titanium dioxide E171

hard gelatin capsule (lid ): titanium dioxide E171; iron dye red oxide E172; gelatin; sodium lauryl sulfate; (body): titanium dioxide E171; iron dye red oxide E172; gelatin; sodium lauryl sulfate

• Hypersensitivity to any component of the drug or to any other ACE inhibitor, including a history of angioedema associated with treatment with ACE inhibitors;

• cardiogenic shock;

• chronic heart failure stage IIB and III;

• simultaneous reception of beta-blockers;

• AV block II Ц III degree (except for patients with an artificial pacemaker);

• acute myocardial infarction;

• sick sinus syndrome (except for patients with an artificial pacemaker);

• acute heart failure;

• atrial fibrillation / flutter;

• WPW and Laun-Ganong-Levin syndrome;

• severe bradycardia;

• severe arterial hypotension;

• impaired renal function (Cl creatinine <30 ml / min);

• pregnancy;

• breastfeeding period;

• age up to 18 years (efficacy and safety have not been established).

With care: aortic stenosis; hypertrophic obstructive cardiomyopathy; impaired liver and / or kidney function; systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma); oppression of bone marrow hematopoiesis; AV block I degree; bradycardia; arterial hypotension; a condition accompanied by a decrease in the BCC (including diarrhea, vomiting); bilateral renal artery stenosis; stenosis of an artery of a single kidney; condition after kidney transplantation; in patients on a salt-restricted diet who are on hemodialysis; combined use with diuretics.

Tradename:

Tarka

Dosage form:

Sustained-release hard gelatin capsules, size No. 0, opaque, pale pink; the contents of the capsules are white granules (trandolapril) and a white tablet (verapamil) of an oblong biconvex shape with a film coating.

Composition:

active substances: trandolapril - 2 mg

excipients: corn starch; lactose monohydrate; povidone (K25); sodium stearyl fumarate

Film-coated tablet:

verapamil hydrochloride - 180 mg

excipients: MCC; sodium alginate; povidone (K30); magnesium stearate; purified water

film coating: hypromellose 6 mPa; hypromellose 15 mPa; hyprolosis 7 mPa; macrogol 400; macrogol 6000; talc; colloidal silicon dioxide; sodium docusat; titanium dioxide E171

hard gelatin capsule (lid ): titanium dioxide E171; iron dye red oxide E172; gelatin; sodium lauryl sulfate; (body): titanium dioxide E171; iron dye red oxide E172; gelatin; sodium lauryl sulfate

Description of the dosage form

Hard gelatinous pale pink opaque capsules (size 0). Capsule contents: white granules (trandolapril), white oblong biconvex tablet of verapamil hydrochloride with a film coating.

Characteristic

Tarka is a combined preparation, which includes long-acting verapamil and trandolapril.

Trandolapril is an ethyl ester of the non-sulfhydryl ACE inhibitor trandolaprilat (prodrug). Verapamil - CCB.

pharmachologic effect

Pharmacological action - antihypertensive .

Pharmacodynamics

Trandolapril

Trandolapril inhibits the activity of the renin-angiotensin-aldosterone system of blood plasma. Renin is an enzyme that is synthesized by the kidneys and enters the bloodstream, where it causes the conversion of angiotensinogen to angiotensin I (an inactive decapeptide). The latter is converted by ACE (peptidyldipeptidase) into angiotensin II, a powerful vasoconstrictor that causes narrowing of the arteries and an increase in blood pressure, as well as stimulating the secretion of aldosterone by the adrenal glands.

Inhibition of ACE leads to a decrease in the concentration of angiotensin II in the blood plasma, which is accompanied by a decrease in vasopressor activity and secretion of aldosterone. Although aldosterone production is not significantly reduced, there may be a slight increase in serum potassium concentration in combination with sodium and water loss.

A decrease in the level of angiotensin II by a feedback mechanism leads to an increase in renin activity in the blood plasma. Another function of ACE is the destruction of kinins (bradykinin), which have a powerful vasodilating property, to inactive metabolites. In this regard, suppression of ACE leads to an increase in circulating and tissue levels of kallikrein-kinins, which promotes vasodilation due to activation of the PG system. This mechanism may partially determine the hypotensive effect of ACE inhibitors and is responsible for some of the side effects.

In patients with arterial hypertension, the use of ACE inhibitors leads to a comparable decrease in blood pressure in the 'sitting' and 'standing' positions without a compensatory increase in heart rate. Peripheral vascular resistance decreases, cardiac output does not change or increases, renal blood flow increases, and glomerular filtration rate usually does not change. Abrupt discontinuation of therapy is not accompanied by a rapid increase in blood pressure. The hypotensive effect of trandolapril appears 1 hour after administration and lasts for at least 24 hours. In some cases, optimal blood pressure control can be achieved only a few weeks after the start of treatment. With prolonged therapy, the hypotensive effect persists. Trandolapril does not impair the circadian blood pressure profile.

Verapamil

Verapamil blocks the transmembrane flow of calcium ions into smooth muscle cells of the myocardium and coronary vessels. Verapamil causes a decrease in blood pressure both at rest and during exercise due to the expansion of peripheral arterioles. As a result of a decrease in OPSS (afterload), myocardial oxygen demand and energy consumption decrease. Verapamil reduces myocardial contractility. The negative inotropic effect of the drug can be compensated for by a decrease in TPVR. The cardiac index does not decrease, with the exception of patients with left ventricular dysfunction.

Verapamil does not affect the sympathetic regulation of cardiac activity, because it does not block beta-adrenergic receptors.

Tarka

In studies on healthy volunteers, there were no signs of interaction between verapamil and trandolapril at the level of pharmacokinetic parameters or the renin-angiotensin system. Therefore, the synergism of the two drugs reflects their complementary pharmacodynamic effects. In clinical trials, the drug Tarka reduced blood pressure to a greater extent than both drugs separately.

Pharmacokinetics

Trandolapril

Trandolapril is rapidly absorbed after oral administration. Absolute bioavailability is about 10%. The time to reach Cmax in blood plasma is about 1 hour.

The binding of trandolapril to blood plasma proteins is about 80% and does not depend on the concentration. The volume of distribution of trandolapril is about 18 liters. T1 / 2 - less than 1 hour. With repeated use, the equilibrium state of concentration is reached after about 4 days both in healthy volunteers and in young and elderly patients with arterial hypertension.

In blood plasma, it undergoes hydrolysis to the formation of an active metabolite trandolaprilate. The time to reach Cmax of trandolaprilat in blood plasma is 4-10 hours. Cmax and AUC do not depend on food intake. The absolute bioavailability of trandolaprilat is about 70%. Binding to blood proteins depends on the concentration and varies from 65% at a concentration of 1000 ng / ml to 94% at a concentration of 0.1 ng / ml. At equilibrium concentration, the effective T1 / 2 of trandolaprilat, together with a small fraction of the drug taken, varies between 16 and 24 hours, which probably reflects binding to plasma and tissue ACE. Trandolaprilat has a high affinity for ACE. 10-15% of the dose of trandolapril is excreted as trandolapril by the kidneys. After ingestion of labeled trandolapril, 33% of radioactivity is found in urine and 66% in feces.In a small amount, it is excreted unchanged through the kidneys (<0.5%).

Renal Cl of trandolaprilat varies from 1 to 4 l / h depending on the dose. The pharmacokinetics of trandolapril have not been studied in children under 18 years of age.

Plasma concentration of trandolapril increases in elderly patients (over 65 years old). However, the plasma concentration of trandolaprilate and its ACE-inhibiting activity in elderly patients of both sexes with arterial hypertension do not change.

Renal failure Compared to healthy volunteers, in patients on hemodialysis and with creatinine Cl of less than 30 ml / min, the plasma concentration of trandolaprilate is approximately 2 times higher, and the renal Cl is reduced by approximately 85%.

Liver failure. Compared to healthy volunteers, in patients with non-severe alcoholic cirrhosis of the liver, the plasma concentration of trandolapril and trandolaprilat increases 9 and 2 times, respectively, but the ACE inhibitory activity does not change.

Verapamil

About 90Ц92% of an oral dose of verapamil is rapidly absorbed in the small intestine. Bioavailability is only 22% due to the pronounced 'first pass' effect through the liver. With repeated use, the average bioavailability can increase up to 30%. The time to reach the peak plasma concentration is 4-15 hours. Equilibrium concentration with repeated use 1 time per day is achieved after 3-4 days. Plasma protein binding is about 90%.

T1 / 2 with repeated use is on average 8 hours; 3-4% of the dose is excreted by the kidneys unchanged. Metabolites are excreted by the kidneys (70%) and through the intestines (16%). One of the 12 metabolites found in urine is norverapamil, the pharmacological activity of which is 10Ц20% of that of verapamil; its share is 6% of the excreted drug. Equilibrium concentrations of norverapamil and verapamil are similar. The pharmacokinetics of verapamil does not change with impaired renal function. The bioavailability and T1 / 2 of verapamil are increased in patients with liver cirrhosis. However, the pharmacokinetics of verapamil does not change in patients with compensated liver dysfunction. Renal dysfunction does not affect the elimination of verapamil.

Tarka

There is no information on the pharmacokinetic interaction of verapamil and trandolapril or trandolaprilat, therefore the pharmacokinetics of the two drugs when used together do not differ from that when they are administered separately.

Indications

• Essential arterial hypertension (for patients for whom combination therapy is indicated).

Contraindications

• Hypersensitivity to any component of the drug or to any other ACE inhibitor, including a history of angioedema associated with treatment with ACE inhibitors;

• cardiogenic shock;

• chronic heart failure stage IIB and III;

• simultaneous reception of beta-blockers;

• AV block II Ц III degree (except for patients with an artificial pacemaker);

• acute myocardial infarction;

• sick sinus syndrome (except for patients with an artificial pacemaker);

• acute heart failure;

• atrial fibrillation / flutter;

• WPW and Laun-Ganong-Levin syndrome;

• severe bradycardia;

• severe arterial hypotension;

• impaired renal function (Cl creatinine <30 ml / min);

• pregnancy;

• breastfeeding period;

• age up to 18 years (efficacy and safety have not been established).

With care: aortic stenosis; hypertrophic obstructive cardiomyopathy; impaired liver and / or kidney function; systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma); oppression of bone marrow hematopoiesis; AV block I degree; bradycardia; arterial hypotension; a condition accompanied by a decrease in the BCC (including diarrhea, vomiting); bilateral renal artery stenosis; stenosis of an artery of a single kidney; condition after kidney transplantation; in patients on a salt-restricted diet who are on hemodialysis; combined use with diuretics.

Application during pregnancy and lactation

The safety of using the drug Tarka in pregnant women has not been established. There are separate observations of pulmonary hypoplasia in newborns, intrauterine growth retardation, patent ductus arteriosus and cranial hypoplasia after the use of ACE inhibitors during pregnancy. ACE inhibitors can cause arterial hypotension, accompanied by anuria in the fetus or newborn, or oligohydroamnion.

The risk of teratogenic effects is highest with the appointment of ACE inhibitors in the II-III trimesters of pregnancy. There is no information on the possible teratogenicity or embryo / fetotoxicity of ACE inhibitors in the first trimester of pregnancy. The use of the drug Tarka during pregnancy is contraindicated.

Verapamil is excreted in breast milk. Trandolapril is contraindicated during breastfeeding. During treatment with Tarka, breastfeeding should be discontinued.

Method of administration and dosage

Inside. The capsule is swallowed whole with water. The drug is best taken in the morning after meals.

The recommended dose for adults is 1 caps. in a day.

Overdose

In clinical studies, the maximum dose of trandolapril was 16 mg. At the same time, there were no signs of his intolerance.

Symptoms of an overdose of the drug Tarka caused by verapamil: a pronounced decrease in blood pressure, AV blockade, bradycardia and asystole.

Overdose deaths have been reported.

Symptoms of an overdose of the drug Tarka caused by trandolapril: a pronounced decrease in blood pressure, shock, stupor, bradycardia, electrolyte disturbances and renal failure.

Treatment: symptomatic.

Treatment of an overdose of verapamil includes parenteral administration of calcium preparations, the use of beta-agonists, and gastric lavage. Given the slow absorption of the prolonged-release drug, patients are observed up to 48 hours; hospitalization may be required during this period.

Verapamil is not removed by hemodialysis.

special instructions

Liver dysfunction

Patients with impaired liver function need careful monitoring during treatment with Tarka.

Arterial hypotension

” больных с неосложненной артериальной гипертензией после приема первой дозы трандолаприла, а также после ее увеличени¤ отмечали развитие артериальной гипотензии, сопровождавшейс¤ клиническими симптомами. –иск артериальной гипотензии выше при нарушении водно-электролитного баланса в результате длительной терапии диуретиками, ограничени¤ потреблени¤ соли, диализа, диареи или рвоты. ” таких больных перед началом терапии трандолаприлом следует прекратить терапию диуретиками и восполнить ќ?  и/или содержание соли. Ќеобходимо контролировать ј? особенно тщательно при назначении или отмене Ќѕ¬ѕ в период применени¤ препарата “арка (см. раздел Ђ¬заимодействиеї).

Ќейтропени¤/агранулоцитоз

ѕри лечении ингибиторами јѕ‘ описаны случаи агранулоцитоза и подавлени¤ функции костного мозга. Ёти нежелательные ¤влени¤ чаще встречаютс¤ у больных с нарушением функции почек, особенно с системными заболевани¤ми соединительной ткани. ” таких пациентов (например с системной красной волчанкой или склеродермией) целесообразно регул¤рно контролировать число лейкоцитов в крови и содержание белка в моче, особенно при нарушении функции почек, лечении кортикостероидами и цитостатиками-антиметаболитами.

јнгионевротический отек

“рандолаприл может вызвать ангионевротический отек лица, ¤зыка, глотки и/или гортани.

—ердечна¤ недостаточность

¬ состав препарата “арка входит верапамил, поэтому применени¤ комбинированного препарата следует избегать у больных с т¤желой дисфункцией левого желудочка (например с фракцией выброса менее 30%, повышением давлени¤ заклинивани¤ легочных капилл¤ров более 20 мм рт. ст. или выраженными симптомами сердечной недостаточности) и больных с любой степенью дисфункции левого желудочка, если они получают бета-адреноблокатор.

ќсобые группы

ѕрепарат “арка не изучалс¤ у детей до 18 лет, поэтому применение его в этой возрастной группе не рекомендуетс¤.

ќбщие меры предосторожности

” некоторых больных, получающих диуретики (особенно недавно), после назначени¤ трандолаприла наблюдаетс¤ резкое снижение ј?.

ѕоскольку данные по взаимодействию верапамила и дизопирамида отсутствуют, дизопирамид не следует примен¤ть в течение 48 ч до или 24 ч после приема верапамила.

Ќарушение функции почек

ѕри обследовании больных артериальной гипертензией следует всегда оценивать функцию почек. ” больных хронической сердечной недостаточностью, двусторонним стенозом почечных артерий или односторонним стенозом почечной артерии у пациентов с единственной почкой (например после ее трансплантации) повышен риск нарушени¤ функции почек, а у больных с почечной недостаточностью Ч риск дальнейшего ухудшени¤ функции почек. ” некоторых больных артериальной гипертензией, не имеющих заболеваний почек, при назначении трандолаприла в комбинации с диуретиком может наблюдатьс¤ повышение азота мочевины в крови и сывороточного креатинина.

vиперкалиеми¤

” больных артериальной гипертензией, особенно с нарушением функции почек, “арка может вызвать гиперкалиемию.

’ирургическое вмешательство/обща¤ анестези¤

ѕри оперативных вмешательствах или общей анестезии с использованием препаратов, вызывающих артериальную гипотензию, трандолаприл может блокировать образование ангиотензина II, св¤занное с компенсаторным выбросом ренина.

ѕри совместном применении верапамила с ингал¤ционными анестетиками, дозировки последних следует подбирать с осторожностью.

 олхицин

—ообщаетс¤ о развитии тетрапареза при одновременном применении верапамила и колхицина. —овместное применение не рекомендуетс¤ (см. раздел Ђ¬заимодействиеї).

¬ли¤ние на способность управл¤ть транспортом и работать с механизмами

—ледует воздерживатьс¤ от управлени¤ автомобилем и от работы с механизмами на ранних этапах лечени¤, поскольку способность к вождению или пользованию сложной техникой может ухудшитьс¤.

”слови¤ хранени¤

ѕри температуре не выше 25 ?C.

’ранить в недоступном дл¤ детей месте.

—рок годности

3 years.

Do not use after the expiration date printed on the package.

Dispensed by prescription.