Tarka modified-release pills 2mg + 180mg 28pcs

Composition

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of 1 tab. contains:

Active ingredients:

trandolapril – 2 mg;

verapamil hydrochloride-180 mg.

Auxiliary substances:

a layer of verapamil hydrochloride – microcrystalline cellulose – 59.1 mg,

sodium alginate – 240 mg,

povidone K30 – 36 mg,

magnesium stearate – 2.4 mg,

water – 22.5 mg;

a layer of trandolapril – corn starch – 74.3 mg,

lactose monohydrate – 107 mg,

povidone K 25 – 10.7 mg,

hypromellose 6 MPa*s (type 2910) – 4 mg,

sodium fumarate – 2 mg.

Composition of the film shell:

hypromellose 6 MPa*s (type 2910) – 11.608 mg, hypromellose 15 MPa*s – 1.152 mg hyprolose 7 MPa*s – 1.152 mg, macrogol 400 – 1.8 mg, macrogol 6000 – 0.322 mg, talc – 1.878 mg, silicon dioxide colloid – 0.03 mg docusate sodium 0.03 mg, titanium dioxide (E171) – 1.912 mg, dye iron oxide red (E 172) – 0.112 mg, dye iron oxide yellow (E 172) – 0.002 mg dye iron oxide black (E 172) – 0.002 mg.

Pharmacological action

Tarka is a combination drug that includes long-acting verapamil and trandolapril.

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

Verapamil hydrochloride is a slow calcium channel blocker.

Trandolapril

Trandolapril inhibits the activity of the renin-angiotensin-aldosterone system in 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 (a low-activity decapeptide). The latter is converted by ACE (peptidyl dipeptidase) into angiotensin II, a powerful vasoconstrictor that causes narrowing of the arteries and increases blood pressure, as well as stimulates the secretion of aldosterone by the adrenal glands.

ACE inhibition leads to a decrease in the concentration of angiotensin II in blood plasma, which is accompanied by a decrease in vasopressor activity and aldosterone secretion. Although the production of aldosterone decreases slightly, however, there may be a slight increase in serum potassium concentration combined with the loss of sodium and water.

A decrease in the concentration of angiotensin II by the feedback mechanism leads to an increase in the activity of renin in blood plasma. Another function of ACE is to break down kinins (bradykinin), which have a powerful vasodilating property, to inactive metabolites. In this regard, ACE inhibition leads to an increase in circulating and tissue concentrations of the kallikrein-kinin system, which contributes to vasodilation due to activation of the prostaglandin system. This mechanism may partially determine the antihypertensive effect of ACE inhibitors and is the cause of some side effects.

In patients with arterial hypertension, the use of ACE inhibitors leads to a comparable decrease in blood pressure in the “lying” and “standing” positions without a compensatory increase in heart rate. OPSS decreases, cardiac output does not change or increases, renal blood flow increases, and glomerular filtration rate usually does not change. Abrupt discontinuation of therapy was not accompanied by a rapid increase in blood pressure.

The antihypertensive effect of trandolapril appears 1 hour after oral use and persists 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 long-term therapy, the antihypertensive effect persists. Trandolapril does not worsen the circadian blood pressure profile.

Verapamil

Verapamil inhibits the flow of calcium ions through the “slow” calcium channels of the membranes of vascular smooth muscle cells, conducting and contractile cardiomyocytes. 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), the myocardial oxygen demand and energy consumption decreases. Verapamil reduces myocardial contractility. The negative inotropic effect of the drug can be compensated by a decrease in OPSS. The cardiac index does not decrease, except in patients with left ventricular dysfunction.

Verapamil does not affect the sympathetic regulation of cardiac activity, since it does not block beta-adrenergic receptors. bronchial asthma and bronchospastic conditions are not contraindications to the use of veralamil.

Tarka

In studies on healthy volunteers, no interaction between verapamil and trandolapril at the level of pharmacokinetic parameters or RAAS was found. Therefore, the synergy of the two drugs reflects their complementary pharmacodynamic effects. In clinical trials, Tarka reduced blood pressure to a greater extent than both drugs alone.

Indications

Arterial hypertension (in patients whose blood pressure is not controlled with trandolapril and verapamil in monotherapy or in patients who are indicated for combination therapy with trandolapril and verapamil in the same dosages).

Use during pregnancy and lactation

Pregnancy The safety of using Tarka in pregnant women has not been established. Use during pregnancy is contraindicated. There are separate observations on the development of pulmonary hypoplasia in newborns, intrauterine growth retardation, open ductus arteriosus, and cranial hypoplasia after the use of ACE inhibitors during pregnancy. There are no reports of teratogenic or embryonic/fetotoxic effects of ACE inhibitors in the first trimester of pregnancy, but this possibility cannot be completely excluded. In patients planning pregnancy, antihypertensive drugs should be prescribed for which the safety of use during pregnancy has been proven, except in cases where the use of ACE inhibitors is necessary. If pregnancy occurs while taking an ACE inhibitor, it should be stopped immediately and a more appropriate treatment should be prescribed. It is known that when using ACE inhibitors in the second and third trimester of pregnancy, fetotoxic effects of drugs (impaired renal function, lack of water, slowing down ossification of the skull bones) and toxic effects on the newborn (renal failure, arterial hypotension, hyperkalemia) are possible. If trandolapril is used starting from the second trimester of pregnancy, ultrasound evaluation of fetal kidney function and cranial condition is recommended. Newborns whose mothers have taken ACE inhibitors during pregnancy should be monitored by a doctor to rule out hypotension. Breast-feeding The use of Tarka during breastfeeding is contraindicated. Verapamil is excreted in breast milk. There are no data on the use of trandolapril during breastfeeding. Preference should be given to drugs with the studied safety profile for this group of patients, especially when feeding newborns and premature babies.

Contraindications

— a history of angioedema associated with the use of ACE inhibitors;

— hereditary and idiopathic angioedema;

— cardiogenic shock;

— chronic heart failure III and IV functional class NYHA classification;

— AV-block II and III degree (except for patients with an artificial pacemaker);

— sinoatrial blockade;

acute myocardial infarction;

— SSSU (except for patients with an artificial pacemaker);

acute heart failure;

— fibrillation/atrial flutter in patients with the syndrome Wolff-Parkinson-white;

— bradycardia;

— severe arterial hypotension;

— severe impairment of renal function;

— pregnancy;

— the period of breastfeeding;

— age under 18 years (effectiveness and safety not established);

— simultaneous use of colchicine and dantrolene;

— aortic stenosis or obstruction of the outflow tract of the left ventricle;

hypertrophic obstructive cardiomyopathy;

— simultaneous use of beta-blockers (in/in) (except for patients undergoing treatment in the intensive care unit);

— lactose intolerance, lactase deficiency, a syndrome of glucose-galactose malabsorption (product contains lactose);

— hypersensitivity to any component of the preparation or to any other ACE inhibitor.

With caution:  hyperkalemia; impaired liver and/or kidney function (creatinine clearance greater than 30 ml/min); with systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), especially during treatment with corticosteroids and antimetabolites; risk of agranulocytosis and neutropenia; inhibition of bone marrow hematopoiesis, grade I AV block; bradycardia; arterial hypotension; conditions accompanied by a decrease in BCC (including diarrhoea, vomiting), bilateral renal artery stenosis, stenosis of the artery of a single kidney (for example, after transplantation), condition after kidney transplantation, diseases accompanied by impaired neuromuscular transmission (myasthenia gravis, Lambert-Eaton syndrome, severe Duchenne muscular dystrophy); in patients who follow a diet with a restriction of table salt; before the procedure of low-density lipoprotein apheresis (LDL), simultaneous desensitizing allergen therapy (for example, hymenopteran venom)-the risk of developing anaphylactoid reactions (in some cases, life – threatening); surgical intervention (general anesthesia) – the risk of excessive blood pressure reduction, hemodialysis using high – flow polyacrylonitrile membranes – the risk of developing anaphylactoid reactions.

Side effects

The following are side effects that may or may not have been associated with taking the drug: Tarka during clinical trials.

Nervous system disorders: frequently (from ≥1/100 to

Disorders of the cardiovascular system: frequently (from ≥1/100 to

Respiratory, thoracic and mediastinal disorders: (≥1/100 to

Gastrointestinal disorders: (≥1/100 to

Common disorders: frequently (from ≥1/100 to

In addition to the reactions identified during clinical trials, the following side effects were identified during post-marketing use::

Infectious diseases: bronchitis.

Disorders of the blood and lymphatic system: leukopenia, thrombocytopenia.

Metabolic disorders: hyperkalemia.

Mental disorders: anxiety, insomnia.

Nervous system disorders: disequilibrium, paresthesia, drowsiness, fainting.

Visual disturbances: visual impairment, “shroud” in front of the eyes.

Labyrinth disorders: dizziness.

Disorders of the cardiovascular system: complete AV block, resting angina, bradycardia, palpitations, tachycardia.

Vascular disorders: arterial hypotension, hyperemia of the skin, flushes of blood to the skin of the face.

Respiratory, thoracic and mediastinal disorders: shortness of breath, nasal congestion.

Gastrointestinal disorders: nausea, diarrhea, dryness of the oral mucosa.

Skin and subcutaneous tissue disorders: Stevens-Johnson syndrome, angioedema, pruritus, rash.

Musculoskeletal and connective tissue disorders: arthralgia, myalgia.

Kidney and urinary tract disorders: pollakiuria, polyuria.

Genital disorders: erectile dysfunction.

Common disorders: chest pain, swelling, weakness.

Laboratory and instrumental data: increased LDH activity, alkaline phosphatase activity, creatinine concentration, urea concentration, ALT activity, and blood AST.

Additional significant side effects observed with verapamil:

Immune system disorders: hypersensitivity.

Endocrine system disorders: hyperprolactinemia.

Cardiac disorders: AV block I, II, III degrees, sinus node arrest (“sinus arrest”), heart failure.

Disorders of the digestive system: gum hyperplasia, abdominal pain, abdominal discomfort.

Skin and subcutaneous tissue disorders: urticaria.

Breast disorders: gynecomastia, galactorrhea.

There are several separate reports of cases of paralysis (tetraparesis) associated with the combined use of verapamil and colchicine. This could be due to colchicine penetration through the BBB due to the suppression of the activity of the CYP 3A4 and P-glycoprotein eoenzymes under the action of verapamil. The combined use of colchicine and verapamil is not recommended.

Additional significant side effects that were observed with the use of turandolapril:

Disorders of the blood and lymphatic system: agranulocytosis.

Immune system disorders: hypersensitivity.

Gastrointestinal disorders: vomiting, abdominal pain, pancreatitis.

Skin and subcutaneous tissue disorders: alopecia.

Common disorders: fever.

Side effects that have been reported with other ACE inhibitors are listed below:

Disorders of the blood and lymphatic system: pancytopenia.

Nervous system disorders: transient cerebrovascular accident.

Cardiac disorders: myocardial infarction, cardiac arrest.

Vascular disorders: brain hemorrhage.

Disorders of the digestive system: intestinal angioedema.

Skin and subcutaneous tissue disorders: erythema multiforme, toxic epidermal necrolysis.

Kidney and urinary tract disorders: acute renal failure.

Laboratory and instrumental data: reduced hemoglobin and hematocrit.

Interaction

Verapamil-related interactions

In vitro studies indicate that verapamil is metabolized by the isoenzymes CYP3A4, CYP1A2, CYP2C8, CYP2C9 and CYP2C18.

Verapamil is a CYP3A4 and P-glycoprotein inhibitor. A clinically significant interaction was observed when used concomitantly with CYP3A4 inhibitors, with an increase in the level of verapamil in blood plasma, while CYP3A4 inducers reduced the concentration of verapamil in blood plasma. Accordingly, with the simultaneous use of such tools, the possibility of this interaction should be taken into account.

Concomitant use of antiarrhythmic drugs and beta-blockers with Tarka may increase the adverse effect on the cardiovascular system (more pronounced AV block, a more significant decrease in heart rate, the development of heart failure and increased arterial hypotension).

Concomitant use of quinidine with Tarka increases the hypotensive effect. Patients with hypertrophic obstructive cardiomyopathy may develop pulmonary edema.

Concomitant use of antihypertensive agents, diuretics and vasodilators with Tarka increases the hypotensive effect.

When used simultaneously with the drug Tarka prazosin, terazosin increases the hypotensive effect.

When used concomitantly with Tarka, some drugs for the treatment of HIV infection (ritonavir) may inhibit the metabolism of verapamil, which leads to an increase in its concentration in blood plasma. When using verapamil concomitantly, the dose should be reduced.

Concomitant use of carbamazepine with Tarka increases the level of carbamazepine in the blood plasma, which may be accompanied by carbamazepine-related side effects-diplopia, headache, ataxia or dizziness.

Concomitant use of lithium with Tarka increases the neurotoxicity of lithium.

When rifampicin is co-administered with Tarka, the hypotensive effect of verapamil may be reduced.

Colchicine is a substrate for the CYP3A4 isoenzyme and P-glycoprotein. Verapamil is known to inhibit the activity of the CYP3A isoenzyme and P-glycoprotein. Therefore, when used concomitantly with verapamil, the concentration of colchicine in the blood can significantly increase. The combined use of drugs is contraindicated.

Hyperkalemia and suppression of myocardial function have been reported in patients with CHD who received verapamil after taking dantrolene. Concomitant use of drugs is contraindicated.

Concomitant use of sulfinpyrazone with Tarka may reduce the hypotensive effect of verapamil.

When used concomitantly with Tarka, the effect of muscle relaxants may increase.

Concomitant use of acetylsalicylic acid as an antiplatelet agent with verapamil may increase the tendency to bleeding.

When used concomitantly with verapamil, the level of ethanol in the blood plasma increases.

Concomitant use with verapamil may lead to an increase in serum levels of simvastatin/atorvastatin/lovastatin.

Patients receiving verapamil should start treatment with HMG-CoA reductase inhibitors (i. e. simvastatin/atorvastatin/lovastatin) at the lowest possible dose, with gradual increases during therapy. If it is necessary to prescribe verapamil to patients who are already receiving HMG-CoA reductase inhibitors, then their doses should be reviewed and reduced accordingly to the concentration of cholesterol in the blood serum.

Fluvastatin, pravastatin, and rosuvastatin are not metabolized by the CYP3A4 isoenzyme, so their interaction with verapamil is least likely.

Trandolapril-related interactions

Diuretics or other antihypertensive medications may increase the antihypertensive effect of trandolapril.

Potassium-sparing diuretics (spironolactone, amiloride, triamterene) or potassium preparations increase the risk of hyperkalemia, especially in patients with renal insufficiency. Trandolapril may reduce potassium loss when co-administered with thiazide diuretics.

Concomitant use of trandolapril (as with any ACE inhibitors) with hypoglycemic agents (insulin or oral hypoglycemic agents) may increase the hypoglycemic effect and lead to an increased risk of hypoglycemia.

Trandolapril may impair the elimination of lithium. It is necessary to monitor the level of lithium in the blood serum.

Other interactions

When using high-flow polyacrylonitrile membranes during hemodialysis in patients treated with ACE inhibitors, anaphylactoid reactions have been described. In patients receiving ACE inhibitors, the use of this type of membrane during hemodialysis should be avoided.

Nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce the hypotensive effect of trandolapril, so when NSAIDs are added to trandolapril therapy or they are discontinued, blood pressure control is necessary.

ACE inhibitors may enhance the antihypertensive effect of certain drugs for inhalation anesthesia.

Allopuripol, cytostatics, immunosuppressants, and systemic corticosteroids or procainamide may increase the risk of leukopenia when treated with ACE inhibitors.

Aitacids may reduce the bioavailability of ACE inhibitors.

The antihypertensive effect of ACE inhibitors may be reduced by co-use of sympathomimetics. In such cases, careful monitoring is necessary.

As with any other antihypertensive medication, co-use of antipsychotics or tricyclic antidepressants increases the risk of orthostatic hypotension.

How to take, course of use and dosage

Adults are prescribed 1 capsule 1 time/day. The drug should be taken orally, preferably in the morning after a meal. The capsule is swallowed whole, washed down with water.

Overdose

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

With an overdose of Tarka, the following symptoms caused by verapamil are possible: a pronounced decrease in blood pressure, AV block, bradycardia, asystole. Overdose deaths have been reported.

Overdose of Tarka may cause the following symptoms caused by prandolapril: marked decrease in blood pressure, shock, stupor, bradycardia, electrolyte disturbances, and renal failure.

Treatment: symptomatic. Treatment for verapamil overdose includes parenteral use of calcium supplements, beta-adrenomimetics, and gastric lavage. Given the delayed absorption of the long-acting drug, the patient’s condition should be monitored for 48 hours; during this period, hospitalization may be required. Verapamil is not removed by hemodialysis.

Description

Modified release tablets, film-coated in pink, oval, with the inscription “Δ182” on one side.

Special instructions

Impaired liver function

Since trandolapril is metabolized in the liver to form an active metabolite, patients with impaired liver function should be prescribed the drug with caution and under close medical supervision.

Arterial hypotension

In patients with uncomplicated arterial hypertension after taking the first dose of trandolapril or increasing the dose of the drug, hypotension was observed, accompanied by clinical symptoms. The risk of hypotension is higher if the water-electrolyte balance is disturbed as a result of prolonged diuretic therapy, salt restriction, dialysis, diarrhea, or vomiting. In such patients, diuretic therapy should be discontinued before starting trandolapril therapy and BCC and/or sodium content should be replenished.

Agranulocytosis/suppression of bone marrow hematopoiesis

Cases of agranulocytosis and suppression of bone marrow function have been reported during treatment with ACE inhibitors. These phenomena are often found in patients with impaired renal function, especially with systemic connective tissue diseases. In such patients (for example, with systemic lupus erythematosus or scleroderma), it is advisable to regularly monitor the number of white blood cells in the blood and the protein content in the urine, especially with impaired renal function, treatment with corticosteroids and antimetabolites.

Angioedema

Trandolapril may cause angioedema of the face, tongue, pharynx, and / or larynx. There is evidence that ACE inhibitors are more likely to cause angioedema in black patients.

Cases of intestinal angioedema have also been reported during treatment with ACE inhibitors. This possibility should be considered if abdominal pain develops (with or without nausea or vomiting) while taking trandolapril.

Heart failure

Tarka contains verapamil, so the use of the combined drug should be avoided in patients with severe left ventricular dysfunction (for example, with a ventricular ejection fraction of less than 30%, increased pulmonary capillary jamming pressure of more than 20 mm Hg, or severe symptoms of chronic heart failure) and in patients with any degree of left ventricular dysfunction, if they receive beta-blockers.

Special patient groups

Tarka has not been studied in children under 18 years of age, so its use in this age group is not recommended.

General precautions

In some patients receiving diuretics (especially in the first days of treatment), after prescribing trandolapril or increasing its dose, a sharp decrease in blood pressure is observed.

Impaired renal function

When examining patients with arterial hypertension, renal function should always be evaluated. In patients with creatinine clearance less than 30 ml / min, lower doses of trandolapril are required.

Patients with impaired renal function, chronic heart failure, bilateral renal artery stenosis, or stenosis of the artery of a single kidney (for example, after its transplantation) have an increased risk of deterioration of renal function. In some patients with arterial hypertension, without impaired renal function, when trandolapril is prescribed in combination with a diuretic, an increase in blood urea nitrogen and serum creatinine may occur.

Hyperkalemia

In patients with arterial hypertension, especially with impaired renal function, Tarka may cause hyperkalemia.

Surgical intervention/General anesthesia

During surgical procedures or general anesthesia with drugs that cause hypotension, trandolapril can block the formation of angiotensin II associated with compensatory renin release.

Desensitization

Patients receiving ACE inhibitors during a course of desensitization (for example, with hymenopteran venom) may develop life-threatening anaphylactic reactions in rare cases.

LDL apheresis

Life-threatening anaphylactic reactions were observed during LDL apheresis in patients receiving ACE inhibitors.

Influence on the ability to drive vehicles and work with mechanisms

Caution should be exercised when driving vehicles and engaging in other potentially dangerous activities that require increased concentration and speed of psychomotor reactions, especially at the beginning of treatment. Tarka may increase the blood alcohol content and slow down its elimination. In this regard, the effects of alcohol can be enhanced.

With impaired renal function

The drug is contraindicated in patients with severe renal impairment (CC).

With caution, the drug should be used for bilateral renal artery stenosis, stenosis of the artery of a single kidney, the condition after kidney transplantation.

With impaired liver function

Caution should be exercised when prescribing the drug to patients with impaired liver function.

Use in children

Contraindicated in children and adolescents under 18 years of age.

Storage conditions

At a temperature not exceeding 25°C. Keep out of reach of children.

Shelf

life is 1 year.

Active ingredient

Verapamil, Trandolapril

Conditions of release from pharmacies

By prescription

Dosage form

long-acting tablets

Purpose

For adults as directed by your doctor

Indications

Hypertension