Tarka, 2 mg+180 mg 28 pcs.

Tarca is a combined antihypertensive drug containing trandolapril (ACE inhibitor) and verapamil (prolonged slow calcium channel blocker).
– Trandolapril:
It is an ethyl ester (prodrug) of trandolaprilate non-sulfhydric ACE inhibitor. Suppresses the activity of the plasma renin-angiotensin-aldosterone system. Renin is an enzyme that is synthesized by the kidneys and enters the bloodstream, where it causes the conversion of angiotensinogen into angiotensin I (inactive decapeptide). The latter is converted by ACE (peptidyl dipeptidase) into angiotensin II, a powerful vasoconstrictor that causes arterial constriction and increases BP and stimulates aldosterone secretion by the adrenals.
ACE inhibition leads to a decrease in angiotensin II plasma concentration, which is accompanied by a decrease in vasopressor activity and aldosterone secretion. Although aldosterone production decreases slightly, there may nevertheless be a slight increase in serum potassium concentration combined with sodium and water loss.
Reduction of angiotensin II levels by a feedback mechanism leads to an increase in plasma renin activity. Another function of ACE is the degradation of kinins (bradykinin), which have a powerful vasodilator property, to inactive metabolites. In this regard, ACE suppression leads to increased circulating and tissue levels of kallikrein-kinins, which contributes to vasodilation through activation of the prostaglandin system. This mechanism probably partially determines the hypotensive 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 BP in sitting and standing positions without a compensatory increase in HR. The RPS is decreased, cardiac output is unchanged or increased. Renal blood flow increases and glomerular filtration rate usually remains unchanged.
Abrupt discontinuation of therapy was not accompanied by a rapid increase in BP. The hypotensive effect of trandolapril is apparent 1 h after oral administration and persists for at least 24 h.
In some cases, optimal BP control is not achieved until several weeks after treatment initiation. With long-term therapy, the hypotensive effect is maintained. Trandolapril does not worsen circadian BP profile.
– Verapamil:
Blocks transmembrane flow of calcium ions into myocardial and coronary vascular smooth muscle cells. Causes a decrease in BP at rest and during physical activity by expanding the peripheral arterioles. As a result of decreased ROS (post-load), myocardial oxygen demand and energy consumption are reduced. Reduces myocardial contractility. Negative inotropic effect of the drug may be compensated by a decrease in ROS. Cardiac index is not reduced, except in patients with left ventricular dysfunction.
Verapamil does not affect sympathetic regulation of cardiac activity, since it does not block β-adrenoreceptors.
– Tarka:
No evidence of interaction between verapamil and trandolapril at the pharmacokinetic or renin-angiotensin system level was found in studies on healthy volunteers. Consequently, the synergism of the two drugs reflects their complementary pharmacodynamic effects. In clinical trials, Tarka reduced BP to a greater extent than both drugs alone.

Indications

Essential arterial hypertension (in patients who are indicated for combination therapy).

Active ingredient

Composition

1 capsule:
– trandolapril (in pellets) 2 mg
– verapamil hydrochloride (in tablets) 180 mg
Excipients: granules – corn starch, lactose monohydrate, povidone (K25), sodium stearyl fumarate; tablets – microcrystalline cellulose, sodium alginate, povidone (K30), magnesium stearate, purified water.

How to take, the dosage

Enally, without chewing (capsule swallowed whole), with a little water, before or after a meal, 1 capsule once a day (morning).

Special Instructions

Patients with impaired liver function require close monitoring during treatment with Tarka.
In patients with uncomplicated arterial hypertension after the first dose of trandolapril, as well as after its increase, the development of arterial hypotension accompanied by clinical symptoms was noted. The risk of arterial hypotension is higher when water-electrolyte balance is impaired as a result of long-term therapy with diuretics, salt restriction, dialysis, diarrhea or vomiting. In such patients, before initiating therapy with trandolapril, diuretic therapy should be discontinued and the BOD and/or salt content should be replenished. BP should be monitored particularly carefully when prescribing or withdrawing NSAIDs during administration of Tarka. (see section “Drug interactions”).
Cases of agranulocytosis and bone marrow suppression have been described during treatment with ACE inhibitors. These adverse events are more common in patients with impaired renal function, especially with systemic connective tissue diseases. In such patients (e.g., with SLE or scleroderma) it is advisable to monitor regularly the number of leukocytes in blood and protein content in urine, especially in renal dysfunction, treatment with GCS and cytostatics-antimetabolites.
Trandolapril may cause angioedema of face, tongue, throat and/or larynx.
The drug Tarka contains verapamil, so the use of the combined drug should be avoided in patients with severe left ventricular dysfunction (e.g., with ejection fraction of 20 mm Hg or marked symptoms of heart failure) and in patients with any degree of left ventricular dysfunction if they receive a beta-adrenoblocker.
Kidney function should always be assessed when examining patients with arterial hypertension. In patients with chronic heart failure, bilateral renal artery stenosis or unilateral renal artery stenosis, patients with a single kidney (e.g., after its transplantation) have an increased risk of impaired renal function, and in patients with renal failure, the risk of further impairment of renal function.
In some patients with arterial hypertension without renal disease, increased blood urea nitrogen and serum creatinine may be observed when trandolapril is prescribed in combination with a diuretic.
In patients with arterial hypertension, especially with impaired renal function, Tarka may cause hyperkalemia.
During surgical interventions or general anesthesia using drugs that cause arterial hypotension, trandolapril may block angiotensin II formation associated with compensatory renin release.
Doses of inhaled anesthetics should be adjusted with caution when used concomitantly with verapamil.
The development of tetraparesis has been reported with concomitant use of colchicine and verapamil. Concomitant use is not recommended (see “Drug Interactions” section).
Some patients receiving diuretics, especially recently, have a sharp decrease in BP after administration of trandolapril.
Since there are no data on interactions between verapamil and disopyramide, disopyramide should not be used for 48 h before or 24 h after taking verapamil.
Pediatric use
The use of Tarca in children under 18 years of age has not been studied, so its use in this age group is not recommended.
Effect on driving and operating machinery
Refrain from driving and operating machinery in the early stages of treatment as the ability to drive or operate complex machinery may be impaired.

Contraindications

– history of angioedema associated with treatment with ACE inhibitors;
– cardiogenic shock;
– chronic heart failure stage IIB and III;
– concomitant use of beta-adrenoblockers;
– AV-blockade of II and III degree (except for patients with pacemakers);
– Acute myocardial infarction;
– CAD (except for patients with pacemakers);
– Acute heart failure;
– atrial fibrillation/thrush;
– Wolff-Parkinson-White syndrome;
– Laun-Hanong-Levin syndrome;
– marked bradycardia;
– marked arterial hypotension;
– renal dysfunction (CK – pregnancy;
– lactation period;
– age under 18 years (efficacy and safety not established);
– known hypersensitivity to any component of Tarka or any other ACE inhibitor.
The preparation should be used with caution in case of aortic stenosis, hypertrophic obstructive cardiomyopathy, liver and/or kidney function disorders, systemic diseases of connective tissue (including SLE, scleroderma), bone marrow hematopoiesis suppression, 1st degree AV-blockade, bradycardia, arterial hypotension, states accompanied by reduction of the circulatory blood flow (including hypertension, scleroderma).

In combination with diarrhea, vomiting, bilateral renal artery stenosis, artery stenosis of the only kidney, post renal transplantation conditions, patients on a salt restricted diet, patients on hemodialysis.

Side effects

Indesirable events reported in clinical trials
The table shows adverse events that had a possible or probable association with the administration of Tarka and were observed in more than 1% of patients in 8 large phase II-III studies. All reactions are categorized by frequency: frequent (>1/100, Nervous system effects: >1/100, Cardiovascular system side: >1/100, Respiratory system side: >1/100, Digestive system disorders: >1/100, Other: >1/100, Other clinically significant adverse events reported in clinical trials and/or clinical practice
Infections: bronchitis.
Blood system disorders: leukopenia, neutropenia, lymphopenia, thrombocytopenia.
Metabolism and nutrition: hyperkalemia, hyponatremia.
Nervous system: balance disorders, insomnia, drowsiness, fainting, hypoesthesia, paresthesia, anxiety, thinking disorders.
Eye: visual disturbances, “fog in front of the eyes”.
Hearing and vestibular system: dizziness, tinnitus.
Cardiovascular system: complete AV-blockade, angina pectoris, bradycardia, palpitations, tachycardia, Gis pedicle block, acute myocardial infarction, ventricular extrasistole, unspecific changes of ST-T segment on ECG, marked BP reduction, blood rushes to the face.
Respiratory system: shortness of breath, sinus congestion.
Gastrointestinal system: nausea, diarrhea, dyspepsia, dry mouth.
Skin and subcutaneous fat: angioedema, skin itching, rash.
Musculoskeletal system: arthralgia, myalgia, gout (hyperuricemia).
Renal and urinary tract: frequent urination, polyuria, hematuria, proteinuria, nicturia.
Sexual system: impotence, endometriosis.
General and local reactions: chest pain, peripheral edema, fatigue.
Laboratory parameters: increase of liver enzymes (AST, ALT, LDH, ALP) and/or bilirubin, serum creatinine, urea residual nitrogen.
Significant adverse events that have been observed with verapamil
Cardiovascular system: AV blockade of I, II, III degree, sinus node arrest, AV dissociation, intermittent claudication, occurrence or aggravation of heart failure, angina, arrhythmia, pulmonary edema, tachycardia, bradycardia, marked arterial hypotension, “flushes” of blood to face.
Nervous system disorders: acute impairment of cerebral circulation, confusion, somnolence, psychotic symptoms, tremor, headache, dizziness, paresthesias.
Hearing and balance: dizziness.
Gastrointestinal tract: gum hyperplasia, abdominal pain or discomfort, reversible nonobstructive bowel obstruction, nausea, vomiting, constipation.
Skin and subcutaneous fat: angioneurotic edema, Stevens-Johnson syndrome, urticaria, purpura, skin itching, ecchymoses, bruising, hair loss, hyperkeratosis, increased sweating, erythema multiforme, maculopapular rash.
Musculoskeletal system: muscle weakness, myalgia, arthralgia.
Reproductive system and breasts: gynecomastia, galactorrhea, impotence.
Immune disorders: hypersensitivity, allergic reactions.
Renal and urinary tract: frequent urination.
General reactions: peripheral edema, fainting, fatigue.
Laboratory indices: hyperprolactinemia, increased liver transaminases activity.
Significant adverse events that were observed during trandolapril use
Blood system: agranulocytosis.
Gastrointestinal: vomiting, abdominal pain, pancreatitis.
Skin and subcutaneous fat: alopecia.
Immune disorders: hypersensitivity.
Urogenital system: decreased libido.
General symptoms: fever.
Adverse events that have been reported with the use of all ACE inhibitors
CNS: transient cerebral circulatory disorders, headache.
Cardiovascular system: myocardial infarction, cardiac arrest, cerebral hemorrhage, arterial hypotension.
Skin and subcutaneous fat: erythema multiforme, toxic epidermal necrolysis, angioedema, rash.
Renal and urinary tract: acute renal failure.
Others: chest pain, cough.
Laboratory parameters: pancytopenia, decreased hemoglobin and hematocrit level, neutropenia, agranulocytosis, hyperkalemia.

Overdose

In clinical trials, the maximum dose of trandolapril was 16 mg. There were no signs of intolerance.
In case of overdose of Tarka the following symptoms caused by verapamil are possible: marked BP decrease, AV-blockade, bradycardia, asystole. The following symptoms caused by trandolapril are possible during overdose: marked BP decrease, shock, stupor, bradycardia, electrolyte disturbances, renal failure.
Treatment: symptomatic. Treatment of verapamil overdose includes parenteral administration of calcium preparations, use of beta-adrenomimetics and gastric lavage. Given the delayed absorption of the prolonged-acting drug, the patient’s condition should be monitored for 48 h; hospitalization may be required during this period. Verapamil is not eliminated by hemodialysis.

Pregnancy use

The drug is contraindicated during pregnancy and lactation.
The safety of the drug Tarka in pregnant women has not been established. There have been some observations of pulmonary hypoplasia in newborns, intrauterine fetal development delay, open arterial duct and skull hypoplasia after use of ACE inhibitors during pregnancy. ACE inhibitors may cause arterial hypotension accompanied by anuria in the fetus or neonate or oligohydroamnion.
The risk of teratogenic effects is highest when ACE inhibitors are prescribed in the second and third trimesters of pregnancy. There is no information about possible teratogenicity or embryo/fetotoxicity of ACE inhibitors in the first trimester of pregnancy.
Verapamil is excreted with breast milk. Breast-feeding should be discontinued during treatment with the drug Tarca.