Universal reference book for medicines
Product name: TARKA (TARKA)

Active substance: trandolapril, verapamil

Type: Antihypertensive drug

Manufacturer: ABBOTT (Germany)
Composition, form of production and packaging
Capsules of prolonged action
hard gelatinous, size No. 0, opaque, pale pink;
the contents of the capsules are white granules (trandolapril) and a white tablet (verapamil) oblong biconvex with a film coating.
1 caps.

Trandolapril (in the composition of granules) 2 mg

verapamil hydrochloride (as part of a tablet) 180 mg

Excipients (granules of trandolapril): corn starch - 37.15 mg, lactose monohydrate - 54.5 mg, povidone K25 - 5.35 mg, sodium stearyl fumarate - 1 mg.

Auxiliary substances (coated verapamil coated tablet): microcrystalline cellulose - 59.1 mg, sodium alginate - 240 mg, povidone K30 - 36 mg, magnesium stearate - 2.4 mg, purified water - 22.5 mg.

The film coating composition of the tablet: hypromellose 6 mPa - 9.576 mg, hypromellose 15 mPa - 0.95 mg, giprolose 7 mPa - 0.944 mg, macrogol 400 - 1.485 mg, macrogol 6000 - 0.266 mg, talc 0.677 mg, silicon colloidal dioxide 0.031 mg, sodium docusate - 0.025 mg, titanium dioxide (E171) - 2.546 mg.

The composition of the hard gelatin capsule body: titanium dioxide (E171) -1.1887 mg, iron oxide red (E172) 0.1008 mg, gelatin 56.7629 mg, sodium lauryl sulfate 0.1176 mg.

Composition of the lid of a hard gelatin capsule: titanium dioxide (E171) - 1.2125 mg, iron dye red oxide (E172) - 0.0672 mg, gelatin - 37.8419 mg, sodium lauryl sulfate - 0.0784 mg.

5 pieces.
- blisters (1) - cardboard boxes.
5 pieces.
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5 pieces.
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5 pieces.
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7 pcs.
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7 pcs.
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7 pcs.
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7 pcs.
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10 pieces.
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10 pieces.
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10 pieces.
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10 pieces.
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14 pcs.
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14 pcs.
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14 pcs.
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14 pcs.
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INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2012.

PHARMACHOLOGIC EFFECT

Combined antihypertensive drug containing trandolapril (ACE inhibitor) and verapamil (long-acting calcium channel blocker of prolonged action).

Trandolapril

It is ethyl ester (prodrug) of non-sulfhydryl inhibitor of ACE trandolaprilate.
Suppresses 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 (low-activity decapeptide). The latter is converted by ACE (peptidyl dipeptidase) into angiotensin II, a potent vasoconstrictor that causes arterial narrowing and increased blood pressure, as well as stimulating the secretion of aldosterone by the adrenal glands.
Inhibition of ACE leads to a decrease in angiotensin II in the blood plasma, which is accompanied by a decrease in vasopressor activity and aldosterone secretion.Although the production of aldosterone decreases slightly, nevertheless, a small increase in potassium concentration in the serum can be observed in combination with the loss of sodium and water.

Reduction of the level of angiotensin II by the feedback mechanism leads to an increase in renin activity in the blood plasma.
Another function of ACE is the destruction of kinin (bradykinin), which has a powerful vasodilating property, to inactive metabolites. In this regard, suppression of ACE leads to an increase in circulating and tissue levels of kallikrein-kinin, which contributes to vasodilation due to the activation of the prostaglandin system. This mechanism, possibly, partially determines the hypotensive effect of ACE inhibitors and is the cause of some side effects.
In patients with hypertension, the use of ACE inhibitors leads to a comparable decrease in blood pressure in the sitting position and standing without compensatory increase in heart rate.
OPSS decreases, cardiac output does not change or increases. Renal blood flow increases, and the rate of glomerular filtration usually remains unchanged.
A sharp discontinuation of therapy was not accompanied by a rapid increase in blood pressure.
The hypotensive effect of trandolapril is manifested 1 hour after ingestion and persists for at least 24 hours.
In some cases, optimal control of BP can be achieved only a few weeks after the start of treatment.
With prolonged therapy, the hypotensive effect persists.Trandolapril does not worsen the circadian profile of blood pressure.
Verapamil

It blocks the transmembrane current of calcium ions in the smooth muscle cells of the myocardium and coronary vessels.
It causes a decrease in blood pressure at rest and with physical exertion due to the expansion of peripheral arterioles. As a result of the decrease in OPSS (afterload), myocardial oxygen demand and energy consumption decrease. Reduces contractility of the myocardium. Negative inotropic effect of the drug can be compensated by a decrease in OPSS. The cardiac index does not decrease, except for patients with left ventricular dysfunction.
Verapamil does not affect sympathetic regulation of cardiac activity, as it does not block β-adrenoceptors.

Tarka

In studies on healthy volunteers, there was no evidence of interaction between verapamil and trandolapril at the pharmacokinetic parameters or the renin-angiotensin system.
Consequently, the synergism of the two drugs reflects their complementary pharmacodynamic effects. In clinical trials, Tarka's drug lowered blood pressure more than both drugs alone.
PHARMACOKINETICS

Trandolapril

Suction

After oral administration, trandolapril is rapidly absorbed.
Absolute bioavailability of about 10%. T max in blood plasma for about 1 h.
Distribution

The binding of trandolapril to plasma proteins is about 80% and is independent of concentration.
V d of trandolapril about 18 liters. T 1/2 <1 h. With repeated use of Css is achieved after about 4 days, both in healthy volunteers, and in patients of young and advanced age with arterial hypertension.
Metabolism

In blood plasma, trandolapril is hydrolyzed to form an active metabolite of trandolaprilate.
T max of trandolaprilat in blood plasma is 4-10 hours. C max or AUC are not dependent on food intake. Absolute bioavailability of trandolaprilate 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. Trandolaprilat has a high affinity for ACE.
Excretion

Renal clearance of trandolaprilat varies from 1 to 4 l / h, depending on the dose.
At C ss, the effective T 1/2 of trandolaprilat, together with a small fraction of the drug taken, varies between 16 h and 24 h, which probably reflects a binding to plasma and tissue ACE. In the form of trandolaprilat, 10-15% of the dose of trandolapril is excreted by the kidneys, <0.5% of the dose is excreted by the kidneys unchanged. After receiving labeled trandolapril, 33% of the radioactivity is detected in urine and 66% in feces.
Pharmacokinetics in special clinical cases

The pharmacokinetics of trandolapril have not been studied in children younger than 18 years.

The concentration of trandolapril in the blood plasma increases in elderly patients (over 65 years).
However, the plasma concentration of trandolaprilate and its ACE inhibitory activity in patients with hypertension of the elderly of both sexes are the same.
Renal failure.
Compared with healthy volunteers, the plasma concentration of trandolaprilat is approximately 2 times higher in patients on hemodialysis and with <30 ml / min, and the renal clearance is reduced by approximately 85%.
Liver failure.
Compared with healthy volunteers in patients with mild alcoholic cirrhosis, the plasma concentration of trandolapril and trandolaprilate increases 9 and 2 times, respectively, but the ACE inhibitory activity does not change.
Verapamil

Suction

After oral administration, about 90-92% of the dose of verapamil is rapidly absorbed into the small intestine.
Bioavailability is only 22% because of the pronounced effect of "first passage" through the liver. With repeated use, the average bioavailability can increase to 30%. The time to reach C max in plasma is 4-15 h.
Distribution

C ss for repeated use 1 time / day is achieved after 3-4 days.
Binding to plasma proteins is about 90%.
Metabolism

One of the 12 metabolites found in urine is noravapamil, whose pharmacological activity is 10-20% of that of verapamil;
its share is 6% of the withdrawn drug. C ss ofnoraveramil and verapamil are similar.
Excretion

T 1/2 for repeated use is an average of 8 hours. 3-4% of the dose is excreted by the kidneys unchanged.
Metabolites are excreted by the kidneys (70%) and through the intestine (16%).
Pharmacokinetics in special clinical cases

The pharmacokinetics of verapamil does not change in renal dysfunction.
Impaired renal function does not affect the excretion of verapamil.
Bioavailability and T 1/2 verapamil increased in patients with cirrhosis of the liver.
However, the pharmacokinetics of verapamil remains unchanged in patients with compensated liver dysfunction.
Tarka

Information on the pharmacokinetic interaction between verapamil and trandolapril / trandolaprilat is not available, so the pharmacokinetics of both drugs in a combined application does not differ from that in their appointment separately.

INDICATIONS

- Essential arterial hypertension (in patients who are shown combined therapy).

DOSING MODE

Adults appoint 1 caps.
1 time / day. The drug should be taken orally, preferably in the morning after eating. Capsule swallowed whole, washed down with water.
SIDE EFFECT

Adverse events recorded in clinical trials

The table shows undesirable events that had an eventual or probable connection with the use of Tark's drug and were observed in more than 1% of patients in 8 large Phase II and III studies.
All reactions are distributed in frequency: frequent (> 1/100, <1/10).
System of organs Frequency Side effects

From the nervous system> 1/100, <1/10 headache, dizziness

From the cardiovascular system> 1/100, <1/10 AV blockade of the I degree

On the part of the respiratory system> 1/100, <1/10 intensification of cough

From the digestive system> 1/100, <1/10 constipation

Other> 1/100, <1/10 asthenia / weakness

Other clinically relevant adverse events reported in clinical trials and / or clinical practice

Infections: bronchitis.

On the part of the hematopoiesis system : leukopenia, neutropenia, lymphopenia, thrombocytopenia.

From the side of metabolism and nutrition: hyperkalemia, hyponatremia.

On the part of the nervous system: imbalance, insomnia, drowsiness, fainting, hypoesthesia, paresthesia, anxiety, impaired thinking.

From the side of the organ of vision: visual impairment, "fog before the eyes".

From the side of the organ of hearing and the vestibular apparatus: dizziness, noise in the ears.

From the cardiovascular system: complete AV blockade, angina, bradycardia, palpitations, tachycardia, blockade of the bundle of the bundle, acute myocardial infarction, ventricular extrasystole, nonspecific changes in the ST-T segment on the ECG, marked decrease in blood pressure, blood tides face.

From the respiratory system: shortness of breath, obstruction of the paranasal sinuses.

From the gastrointestinal tract: nausea, diarrhea, indigestion, dyspepsia, dry mouth.

From the skin and subcutaneous fat: angioedema, skin itching, rash.

From the musculoskeletal system: arthralgia, myalgia, gout (hyperuricemia).

From the side of the kidneys and urinary tract: frequent urination, polyuria, hematuria, proteinuria, nocturia.

On the part of the reproductive system: impotence, endometriosis.

General and local reactions: chest pain, peripheral edema, fatigue.

Laboratory indicators: elevation of hepatic enzymes (AST, ALT, LDH, AP) and / or bilirubin, serum creatinine, residual urea nitrogen.

Significant adverse events that were observed with verapamil

Cardiovascular system: AV blockade I, II, III degree, sinus node stop, AV dissociation, intermittent claudication, occurrence or weighting of heart failure, angina pectoris, arrhythmia, pulmonary edema, tachycardia, bradycardia, severe arterial hypotension, "hot flashes "blood to face.

From the nervous system: acute disturbance of cerebral circulation, confusion, drowsiness, psychotic symptoms, tremor, headache, dizziness, paresthesia.

From the side of the organ of hearing and balance: dizziness.

From the digestive tract: gingival hyperplasia, pain or discomfort in the abdomen, reversible obstructive intestinal obstruction, nausea, vomiting, constipation.

From the skin and subcutaneous fat: angioneurotic edema, Stevens-Johnson syndrome, urticaria, purpura, pruritus, ecchymosis, bruising, hair loss, hyperkeratosis, increased sweating, erythema multiforme, maculopapular rash.

From the musculoskeletal system: muscle weakness, myalgia, arthralgia.

From the side of the reproductive system and the mammary glands: gynecomastia, galactorrhea, impotence.

Immune disorders: hypersensitivity, allergic reactions.

From the side of the kidneys and urinary tract: frequent urination.

General reactions: peripheral edema, fainting, fatigue.

Laboratory indicators: hyperprolactinemia, increased activity of hepatic transaminases.

Significant adverse events that were observed with the use of trandolapril

From the side of the hematopoiesis system: agranulocytosis.

From the gastrointestinal tract: vomiting, abdominal pain, pancreatitis.

From the skin and subcutaneous fat: alopecia.

Immune disorders: hypersensitivity.

From the genitourinary system: a decrease in libido.

Common symptoms: fever.

Adverse events that are registered with the use of all ACE inhibitors

From the side of the central nervous system: transient impairment of cerebral circulation, headache.

From the cardiovascular system: myocardial infarction, cardiac arrest, cerebral hemorrhage, arterial hypotension.

From the skin and subcutaneous fat: multiforme exudative erythema, toxic epidermal necrolysis, angioedema, rash.

From the side of the kidneys and urinary tract: acute renal failure.

Others: chest pain, cough.

Laboratory indicators: pancytopenia, reduction of hemoglobin and hematocrit, neutropenia, agranulocytosis, hyperkalemia.

CONTRAINDICATIONS

- history of angioedema, associated with treatment with ACE inhibitors;

- cardiogenic shock;

- chronic heart failure of IIB and III stage;

- simultaneous use of beta-blockers;

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

acute myocardial infarction;

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

- acute heart failure;

- atrial fibrillation / flutter;

- Wolff-Parkinson-White syndrome;

- Laun-Ganong-Levin syndrome;

- pronounced bradycardia;

- severe arterial hypotension;

- impaired renal function (CK <30 ml / min.);

- Pregnancy;

- the period of breastfeeding;

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

- known hypersensitivity to any component of the drug or to any other ACE inhibitor.

With caution should be used in aortic stenosis, hypertrophic obstructive cardiomyopathy, liver and / or kidney dysfunction, systemic connective tissue diseases (including SLE, scleroderma), oppression of bone marrow hematopoiesis, AV-blockade of I degree, bradycardia, arterial hypotension , conditions accompanied by a decrease in BCC (including diarrhea, vomiting), bilateral stenosis of the renal arteries, stenosis of the artery of a single kidney, a condition after kidney transplantation, in patients observing a diet from ophthalmic
icheniem salts, hemodialysis, with the concomitant use of diuretics.
PREGNANCY AND LACTATION

Contraindicated use of the drug during pregnancy and during lactation.

The safety of the use of the drug Tark in pregnant women is not established.
There are separate observations of lung hypoplasia in newborns, intrauterine growth retardation of the fetus, open ductus arteriosus and skull 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 in the appointment of ACE inhibitors in the II and III trimesters of pregnancy.
Information about the possible teratogenicity or embryo / fetotoxicity of ACE inhibitors in the I trimester of pregnancy is not available.
Verapamil is excreted in breast milk.
During treatment with Tarka, breastfeeding should be discontinued.
APPLICATION FOR FUNCTIONS OF THE LIVER

Contraindicated use of the drug in violation of kidney function (QC <30 ml / min.).

Caution should be applied to the drug with bilateral stenosis of the renal arteries, stenosis of the artery of a single kidney, the condition after kidney transplantation.

APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS

With caution should prescribe the drug to patients with impaired liver function.

APPLICATION FOR CHILDREN

Contraindicated in children and adolescents under 18 years.

SPECIAL INSTRUCTIONS

Patients with a violation of the liver need to be closely monitored during treatment with Tarka.

In patients with uncomplicated hypertension After the first dose of trandolapril and after the increase it noted the development of arterial hypotension, accompanied by clinical symptoms. The risk of arterial hypotension higher in violation of water and electrolyte balance as a result of prolonged diuretic therapy, limiting salt intake, dialysis, diarrhea or vomiting. In these patients before starting therapy should discontinue trandolapril therapy with diuretics and fill BCC and / or salt content. It is necessary to monitor blood pressure carefully during the appointment or termination of NSAIDs during the period of application of the drug Tarka. (See. The section "Patient interaction").
In the treatment of cases of agranulocytosis and bone marrow suppression described ACE inhibitors. These adverse events were more common in patients with impaired renal function, especially with systemic connective tissue diseases. In such patients (e.g., scleroderma or SLE) advisable to regularly monitor the number of leukocytes in the blood and the protein content in urine, especially with impaired renal function, the treatment of cytostatics and corticosteroids, antimetabolites.
Trandolapril may cause angioneurotic edema of the face, tongue, pharynx, and / or the larynx.
The preparation Tarka includes verapamil, therefore, of the combined drug should be avoided in patients with severe left ventricular dysfunction (e.g., ejection fraction <30%, increased pulmonary capillary wedge pressure> 20 mm Hg. V. Or symptomatic heart failure) and patients with any degree of left ventricular dysfunction if they are receiving a beta-blocker.
In a study of patients with hypertension should always evaluate kidney function. In patients with chronic heart failure, bilateral renal artery stenosis or unilateral renal artery stenosis in patients with a solitary kidney (eg, after transplantation) are at increased risk of renal dysfunction and in patients with renal failure - the risk of further deterioration of renal function.
In some patients with hypertension, renal diseases have not when assigning trandolapril in combination with a diuretic can be observed increase in blood urea nitrogen and serum creatinine.
In patients with hypertension, especially with impaired renal function, Tarka medication can cause hyperkalemia.
During surgery or general anesthesia using drugs that cause hypotension, trandolapril can block the formation of angiotensin II, associated with compensatory renin release.
Precautions should titrate doses of inhaled anesthetics while the use of verapamil.
With simultaneous use of verapamil and colchicine reported tetraparesis development. The combined use is not recommended (see. The section "Patient interaction").
Some patients receiving diuretics, especially recently, following the appointment of trandolapril has been a sharp decrease in blood pressure.
Since data on the interaction of verapamil and disopyramide absent, disopyramide not be used within 48 hours before or 24 hours after administration of verapamil.
Use in Pediatrics

Tarka has been studied not use the drug in children under 18 years of age , therefore its use in this age group is not recommended.
Impact on the ability to drive vehicles and manage mechanisms

Should refrain from driving and using machinery from the early stages of treatment, because the ability to drive or use complex technology may deteriorate.
OVERDOSE

In clinical studies, the maximum dose was 16 mg of trandolapril. In this case, there were no signs of his intolerance.
If overdose Tarka, the following symptoms caused by verapamil : marked reduction of blood pressure, AV-block, bradycardia, asystole. Cases of death from overdose.
If overdose Tarka, the following symptoms caused by trandolapril : marked reduction of blood pressure, shock, stupor, bradycardia, electrolyte disturbances, renal failure.
Treatment:symptomatic. Treatment of overdoses of verapamil comprises parenteral administration of calcium preparations, the use of beta-agonists and gastric lavage. Given the slow absorption of the drug depot, the patient should be monitored for 48 hours; During this period may require hospitalization. Verapamil is not removed in hemodialysis.
DRUG INTERACTION

Interactions caused verapamil
Studies in vitro indicate that verapamil is metabolized by the action of isozymes CYP3A4, CYP1A2, CYP2C8, CYP2C9 and CYP2C18.
Verapamil is an inhibitor of CYP3A4. Clinically significant interaction was observed while the use of CYP3A4 inhibitors, the observed increase in plasma verapamil, while inducers of CYP3A4 verapamil decreased concentration in the blood plasma. Accordingly, while the use of such means should be considered the possibility of interaction.
The following table summarizes the drug interaction caused verapamil.
A drug The possible effect on verapamil or verapamil to another drug while applying
Alpha-blockers
Prazosin Increase in C max of prazosin (40%), no effect on T 1/2 prazosin.
Increased AUC terazosin terazosin (24%) and C max (25%).
Antiarrhythmics
Flecainide Minimal effect on flecainide plasma clearance (<10%); no effect on verapamil plasma clearance.
Quinidine, quinidine Reduced oral clearance (35%).
Means for treating bronchial asthma
Theophylline Reduction oral and systemic clearance (20%). Smokers - a decline of 11%.
anticonvulsants
Carbamazepine Increased carbamazepine AUC (46%) in patients with refractory partial epilepsy.
Antidepressants
Imipramine Increased AUC imipramine (15%) did not affect the level of the active metabolite desipramine.
Hypoglycemic agents for oral
Glyburide increasing C max glyburide (28%), AUC (26%).
Antiinfectives
erythromycin may increase the level of verapamil.
Rifampicin Reduced AUC (97%), C max (94%), bioavailability (92%) of verapamil.
Telithromycin may increase levels of verapamil.
Antineoplastic
Doxorubicin increases AUC (89%) and C max(61%) of doxorubicin inside the verapamil when taking in patients with small cell lung cancer. Introduction of verapamil / in patients with advanced tumors no effect on the plasma clearance doxirubicin.
Barbiturates
Phenobarbital Increased verapamil oral clearance - 5 times.
Benzodiazepines and other anxiolytics
Buspirone increases AUC and the C max of buspirone in 3.4 times.
Midazolam increases AUC (3 times) and C max (2 times) midazolam.
Beta-blockers
metoprolol increases AUC (32.5%) and C max (41%) of metoprolol in patients with angina pectoris.
Propranolol increases AUC (65%) and C max(94%) of propranolol in patients with angina pectoris.
Cardiac glycosides
Digitoxin Reduced total clearance (27%) and extrarenal clearance (29%) of digitoxin.
Digoxin: In healthy volunteers, increased the C max (% on 45-53), the C ss (42%) and AUC (52%) of digoxin.
Blockers of histamine H 2 -receptors
cimetidine increases AUC R- and S-verapamil (25% and 40%, respectively) with decreasing clearance R- and S-verapamil.
Immunological agents
Tacrolimus increases AUC, C ss , C max (45%) of cyclosporin.
Sirolimus may increase sirolimus levels.
Tacrolimus may increase tacrolimus levels.
Lipid-lowering agents, HMG-CoA reductase inhibitor
atorvastatin may increase the level of atorvastatin.
Lovastatin may increase the level of lovastatin.
Simvastatin increases AUC (2.6 fold) and C max (4.6 times) of simvastatin.
Serotonin receptor antagonists
almotriptan increases AUC (20%) and C max (24%) of almotriptan.
Uricosuric agents
sulphinpyrazone Increased verapamil oral clearance (3 times), reducing its bioavailability (60%).
Other
Grapefruit juice Increased AUC R- and S-verapamil (49% and 37%, respectively) and C maxR- and S-verapamil (75% and 51% respectively). T 1/2 and renal clearance did not change.
St. John's wort Reduced AUC R- and S-verapamil (78% and 80%, respectively) with decreasing C max.
Other possible interaction
At simultaneous application with the drug Tarka antiarrhythmics and beta-blockers may increase the adverse effects on the cardiovascular system (more pronounced AV-block, a significant decrease in heart rate, heart failure and increased arterial hypotension).
When applied simultaneously with the drug Tarka quinidine enhanced hypotensive effect. In patients with hypertrophic obstructive cardiomyopathy may develop pulmonary edema.
With simultaneous use of antihypertensive drugs, diuretics and vasodilators with drug Tarka enhanced hypotensive effect.
When applied simultaneously with the drug Tarka prazosin, terazosin enhanced hypotensive effect.
When applied simultaneously with the drug Tarka certain drugs for treatment of HIV infection (ritonavir) may inhibit the metabolism of verapamil, which leads to an increase in its concentration in plasma. With simultaneous use of verapamil dose should be reduced.
At simultaneous application with carbamazepine drug Tarka increased carbamazepine plasma levels that may be associated with side effects typical of carbamazepine - diplopia, headache, ataxia or dizziness.
When applied simultaneously with the drug lithium Tarka increased neurotoxicity lithium.
With simultaneous use of rifampicin with drug Tarka may decrease the hypotensive effect of verapamil.
At simultaneous application with sulfinpirazona drug Tarka may decrease the hypotensive effect of verapamil.
While the use of a muscle relaxant drug Tarka effect may increase.
With simultaneous use of acetylsalicylic acid, verapamil increased bleeding.
While the use of verapamil in plasma ethanol levels rise.
The simultaneous use of verapamil may lead to increased serum levels of simvastatin or lovastatin.
Patients receiving verapamil treatment inhibitors of HMG-CoA reductase inhibitors (i.e., simvastatin / lovastatin) should start with the lowest possible dose with gradual increase in the course of their treatment. If you want to assign verapamil to patients already receiving HMG-CoA reductase, it is necessary to reconsider and reduce their dose, respectively, the concentration of cholesterol in the blood serum. Such tactics should be followed, while the appointment of verapamil with atorvastatin.
Fluvastatin, pravastatin and rosuvastatin are not metabolized by the action of the isoenzyme CYP3A4, however their interactions with verapamil least likely.
Interactions caused trandolapril
Hypotensive diuretics or other drugs may enhance the hypotensive effect of trandolapril. Trandolapril can reduce the loss of potassium in the combined use with thiazide diuretics.
Potassium-sparing diuretics (spironolactone, amiloride, triamterene) or potassium drugs increase the risk of hyperkalemia while the use of trandolapril.
The simultaneous use of trandolapril (such as ACE inhibitors and any) with hypoglycaemic drugs (insulin or oral hypoglycemic agents) can enhance the hypoglycemic effect and lead to increased risk of hypoglycemia.
Trandolapril may worsen lithium removal. Necessary to monitor the level of lithium in blood serum.
other interactions
While the use of verapamil colchicine concentration in the blood can rise significantly, since the latter is a substrate for CYP3A and P-glycoprotein, which, in turn, inhibit the metabolism of verapamil.
In animal experiments it was shown that inhaled anesthetics reduce the intake of calcium into the cell, providing a dampening effect on the cardiovascular system. With simultaneous use of verapamil may increase inhibitory effect on the myocardium.
The hypotensive effect of certain anesthetic gases can be enhanced ACE inhibitors.
When used during dialysis vysokoprotochnyh polyacrylonitrile membranes in patients treated with ACE inhibitors, anaphylactoid reactions have been described.Patients taking ACE inhibitors should be avoided in these membranes during hemodialysis.
NSAIDs reduce the hypotensive effect of trandolapril.
Cytotoxic or other immunosuppressive drugs and corticosteroids increase the risk of leukopenia when used in conjunction with ACE inhibitors.
TERMS OF RELEASE FROM PHARMACY

The drug is released by prescription.

TERMS AND CONDITIONS OF STORAGE

The drug should be stored out of the reach of children at a temperature of no higher than 25 ° C.
Shelf life - 3 years.
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