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
Modified-release tablets covered with a
pink film cover , oval, engraved "? 182" on one side.

1 tab.

Trandolapril 2 mg

verapamil hydrochloride 180 mg

[PRING] 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;
layer of trandolapril - corn starch - 74.3 mg, lactose monohydrate - 107 mg, povidone K25 - 10.7 mg, hypromellose 6 mPa * s (type 2910) - 4 mg, sodium stearyl fumarate - 2 mg.
Composition of the film membrane: hypromellose 6 mPa * s (type 2910) - 11.608 mg, hypromellose 15 mPa * s - 1.152 mg, giprolose 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, iron oxide red oxide (E172) 0.112 mg, iron oxide yellow oxide (E172) 0.002 mg, ferric oxide black oxide (E172) 0.002 mg.

14 pcs.
- blisters (1) - packs of cardboard.
14 pcs.
- blisters (2) - packs of cardboard.
14 pcs.
- blisters (4) - packs of cardboard.
14 pcs.
- blisters (7) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2014.

PHARMACHOLOGIC EFFECT

Tarka is a combined drug, which includes verapamil prolonged action and trandolapril.

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

Verapamil hydrochloride is a blocker of slow calcium channels (BCCC).

Trandolapril

Trandolapril 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.

Reducing the concentration 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 concentrations of the kallikrein-kinin system, which contributes to vasodilation by activating 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 "lying" and "standing" positions 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 does not change. A sharp discontinuation of therapy was not accompanied by a rapid increase in blood pressure.
The antihypertensive 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 initiation of treatment.
With prolonged therapy, the hypotensive effect persists. Trandolapril does not worsen the circadian profile of blood pressure.
Verapamil

Verapamil inhibits the current of calcium ions through the "slow" calcium channels of membranes of smooth muscle cells of vessels, 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 the decrease in OPSS (afterload), myocardial oxygen demand and energy consumption decrease. Verapamil reduces myocardial contractility. 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.
bronchial asthma and bronchospastic states are not contraindications to the appointment of veralamyl.
Tarka

In studies on healthy volunteers, there was no evidence of interaction between verapamil and trandolapril at the pharmacokinetic parameters or RAAS.
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 ingestion, trandolapril is rapidly absorbed.
Absolute bioavailability of about 10%. TC max in blood plasma for about 1 hour.
Distribution

The association of trandolapril with plasma proteins is about 80% and does not depend on concentration.
V d of trandolapril about 18 liters. T 1/2 <1 h. With repeated use of C ss is achieved after about 4 days, both in healthy volunteers, and in patients of young and elderly age with hypertension.
Metabolism

In blood plasma, trandolapril is hydrolyzed to form an active metabolite of trandolaprilate.
TC max of trandolaprilat in blood plasma is 3-8 hours. C max and AUC are not dependent on food intake. Absolute bioavailability of trandolapril by taking trandolapril about 13%. The association with 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). In an equilibrium state, the concentration of the effective T 1/2 of trandolaprilat together with a small fraction of the drug taken varies between 15 hours and 23 hours, which probably reflects binding to plasma and tissue ACE.
Excretion

Trandolaprilat has a high affinity for ACE.
9-14% of the dose of trandolapril is excreted as trandolaprilate by the kidneys. After receiving labeled trandolapril, 33% of the drug was excreted by the kidneys and 66% by the intestine. In a small amount, it is excreted unchanged through the kidneys (less than 0.5%).
Renal clearance of trandolaprilat varies from 0.15 to 4 l / h, depending on the dose.

Pharmacokinetics in special clinical cases

Children.
The pharmacokinetics of trandolapril have not been studied in children under 18 years of age.
Elderly patients.
The concentration of trandolapril in blood plasma increases in elderly patients with hypertension (over 65 years). However, the plasma concentration of trandolaprilate and its ACE inhibitory activity in patients with hypertension of the elderly and young patients are the same. The pharmacokinetics of trandolapril and trandolaprilate, as well as ACE inhibitory activity in elderly patients 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%. Patients with renal failure are recommended to correct the dose of the drug.
Liver failure.
Compared with healthy volunteers in patients with alcoholic cirrhosis, the plasma concentration of trandolapril and trandolaprilate increases 9 and 2 times, respectively, but the ACE inhibitory activity does not change. Patients with hepatic insufficiency may require the administration of smaller doses of the drug.
Verapamil

Suction

About 90% of the intravenous 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%. Eating does not affect the bioavailability of the drug. TC max is 4-15 hours. The maximum plasma concentration of noraveramil is reached approximately 5-15 hours after taking the drug.
Distribution

C ss for repeated use 1 time / day is achieved after 3-4 days.
The connection with 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

There is no information on the pharmacokinetic interaction between verapamil and trandolapril / trandolaprilate, therefore 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

Below are the side effects that had a possible or probable connection with the use of Tark's drug during clinical trials.

Disturbances from the nervous system: often (from? 1/100 to <1/10): headache, dizziness.

Disorders from the cardiovascular system: often (from? 1/100 to <1/10): AV-blockade of the I degree.

Disturbances from the respiratory system, chest and mediastinal organs: (from? 1/100 to <1/10): cough.

Disorders from the digestive tract: (from? 1/100 to <1/10): constipation.

General disorders: often (from? 1/100 to <1/10): asthenia.

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

Infectious diseases: bronchitis.

Violations from the blood and lymphatic system: leukopenia, thrombocytopenia.

Disorders from the metabolism: giperkaliemia.

Disorders of the psyche: anxiety, insomnia.

Disturbances from the nervous system: imbalance, paresthesia, drowsiness, fainting.

Disorders from the side of the organ of vision: visual impairment, "shroud" before the eyes.

Labyrinthine disorders: dizziness.

Disorders from the cardiovascular system: complete AV blockade, restless stenocardia, bradycardia, sensation

palpitations, tachycardia.

Violations from the vessels: arterial hypotension, hyperemia of the skin, blood rushes to the skin of the face.

Disturbances from the respiratory system, chest and mediastinal organs: shortness of breath, nasal congestion.

Disorders from the digestive tract: nausea, diarrhea, dryness of the oral mucosa.

Disturbances from the skin and subcutaneous tissues: Stevens-Johnson syndrome, angioedema, skin itching, rash.

Disturbances from the musculoskeletal and connective tissue: arthralgia, myalgia.

Disorders from the kidneys and urinary tract: pollakiuria, polyuria.

Violations of the genitals: erectile dysfunction.

Common disorders: chest pain, swelling, weakness.

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

Additional significant side effects that were observed with verapamil:

Impaired immune system: hypersensitivity.

Disorders from the endocrine system: hyperprolactinaemia.

Violations from the heart: AV-blockade I, II, III degree, stopping the sinus node ("sinus arrest"), heart failure.

Disorders from the digestive system: gingival hyperplasia, abdominal pain, discomfort in the abdomen.

Disturbances from the skin and subcutaneous tissues: urticaria.

Breast disorders: gynecomastia, galactorrhea.

There are several separate reports about cases of development of paralysis (tetraparesis) associated with joint application

verapamil and colchicine.
This could be due to the penetration of colchicine through the BBB in connection with the suppression of the activity of the CYP 3A4 and P-glycoprotein activity 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 trandolapril:

Violations from the blood and lymphatic system: agranulocytosis.

Impaired immune system: hypersensitivity.

Disorders from the digestive tract: vomiting, abdominal pain, pancreatitis.

Disturbances from the skin and subcutaneous tissues: alopecia.

General disorders: fever.

The following are side effects that have been reported with other ACE inhibitors:

Violations from the blood and lymphatic system: pancytopenia.

Disorders from the nervous system: transient impairment of cerebral circulation.

Impaired heart: myocardial infarction, cardiac arrest.

Vascular disorders: cerebral hemorrhage.

Disorders from the digestive system: intestinal angioedema.

Disturbances from the skin and subcutaneous tissues: erythema multiforme, toxic epidermal necrolysis.

Disorders from the kidneys and urinary tract: acute renal failure.

Laboratory and instrumental data: reduction of hemoglobin and hematocrit.

CONTRAINDICATIONS

- angioedema in history, associated with the administration of ACE inhibitors;

- hereditary and idiopathic edema of Quincke;

- cardiogenic shock;

- chronic cardiac insufficiency III and IV of the functional class according to NYHA classification;

- AV blockade 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;

- atrial fibrillation / flutter in patients with Wolff-Parkinson-White syndrome;

- pronounced bradycardia;

- severe arterial hypotension;

- severe renal dysfunction (CK <30 ml / min);

- Pregnancy;

- the period of breastfeeding;

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

- simultaneous reception with colchicine and dantrolene;

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

- hypertrophic obstructive cardiomyopathy;

- simultaneous use with beta-blockers (IV) (for

excluding patients under treatment in the intensive care unit);

- lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome (the preparation contains lactose);

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

With caution: hyperkalemia;
disrupting liver function
and / or kidney function (QC more than 30 ml / min);
with system
diseases of connective tissue (including systemic lupus erythematosus, scleroderma) especially in the background of treatment

corticosteroids and antimetabolites;
risk of agranulocytosis and neutropenia; oppression of bone marrow hematopoiesis, AV-blockade of the 1st degree; bradycardia;arterial hypotension; (including diarrhea, vomiting), bilateral stenosis of the renal arteries, stenosis of the artery of a single kidney (for example, after transplantation), a condition after kidney transplantation, diseases accompanied by a violation of neuromuscular transmission (myasthenia gravis, syndrome Lambert-Eaton, Duchenne's severe muscular dystrophy); in patients who observe a diet with restriction of table salt; before the procedure of apheresis of low density lipoproteins (LDL), simultaneous
the conduct of desensitizing therapy with allergens (for example, Hymenoptera venom) - the risk of anaphylactoid reactions (in some cases, life-threatening);
surgical intervention (general anesthesia) - the risk of developing excessive
reduction of blood pressure, hemodialysis using high-flow polyacrylonitrile membranes - the risk of developing anaphylactoid

reactions.

PREGNANCY AND LACTATION

Pregnancy

The safety of the use of the drug Tark in pregnant women is not established.
Application during pregnancy is contraindicated.
There are separate observations on the development of lung hypoplasia in newborns, intrauterine growth retardation of the fetus, open arterial duct and hypoplasia of the bones of the skull after the use of ACE inhibitors during

pregnancy.

There is no information on teratogenic or embryo / fetotoxic effects of ACE inhibitors in the first trimester of pregnancy, but this possibility can not be completely ruled out.
Patients planning a pregnancy should be prescribed antihypertensive drugs for which safety of use during pregnancy has been proven, except when the use of ACE inhibitors is necessary. If pregnancy occurs during the administration of an ACE inhibitor, it must be immediately discontinued and a more appropriate treatment should be prescribed.
It is known that with the use of ACE inhibitors in the second and third trimester of pregnancy, it is possible fetotoxic

exposure to the drugs (renal failure, oligohydramnios, slowing ossification of bones of the skull) and toxic effects on newborn (renal failure, hypotension, hyperkalaemia). In the case of trandolapril, starting from the second trimester of pregnancy, the fetus is recommended ultrasound assessment of renal function and status of the skull. Newborns whose mothers during pregnancy have taken ACE inhibitors should be under a doctor's supervision in order to avoid hypotension.
Breastfeeding period
Application Tarka drug during breast feeding is contraindicated. Verapamil is released in breast milk.
Data on the use of trandolapril during breastfeeding are not available. Preference should be given to drug-studied safety profile for this group of patients, especially when feeding newborns and premature babies.
APPLICATION FOR FUNCTIONS OF THE LIVER

Do not use this drug in severe renal impairment (creatinine clearance <30 mL / min.).
With care use in patients with bilateral renal artery stenosis, stenosis of the artery only kidney condition after kidney transplantation.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS

Precautions should be prescribed to patients with impaired liver function.
APPLICATION FOR CHILDREN

Contraindicated in children and adolescents under 18 years.

SPECIAL INSTRUCTIONS

Abnormal liver function
As trandolapril metabolized in the liver to form the active metabolite, drug patients with impaired liver function should be used with caution and with careful medical supervision.
Hypotension
For patients with uncomplicated hypertension after the first dose trandolapril or increasing doses noted development of 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 therapy trandolapril discontinue therapy with diuretics and fill the BCC and / or sodium.
Agranulocytosis / inhibition of bone marrow hematopoiesis
When treating cases of agranulocytosis and bone marrow suppression functions are described ACE inhibitors. These phenomena are more likely to
occur in patients with impaired renal function, especially with systemic connective tissue diseases.
Have
such patients (e.g., systemic lupus erythematosus or scleroderma) advisable to regularly monitor the
number of leukocytes in the blood and the protein content in urine, especially when the kidney function, antimetabolites and corticosteroids.
Angioedema
Trandolapril may cause angioneurotic edema of the face, tongue, pharynx, and / or the larynx. There is evidence that ACE inhibitors are more likely to cause angioedema in patients blacks.
Against the background of treatment with ACE inhibitors are also cases of angioneurotic edema of the intestine were observed. This possibility should be taken into account in the development of abdominal pain (accompanied by nausea or vomiting, or without symptoms) in patients receiving trandolapril.
Heart failure
The preparation Tarka includes verapamil, therefore use of combined ppepapata should be avoided in patients with severe left ventricular dysfunction (e.g., ventricular ejection fraction less than 30%, increased pulmonary capillary wedge pressure greater than 20 mm Hg or symptomatic congestive heart failure) and in patients with any degree of left ventricular dysfunction if they are receiving beta-blockers.
Special groups of patients
drug Tarka has not been studied in children under 18 years of age, therefore its use in this age group is not recommended.
General precautions
Some patients receiving diuretics (especially in the first days of treatment), after administration of trandolapril or increasing the dose, there is a sharp decrease in blood pressure.
Impaired Renal Function
In a study of hypertensive patients should always evaluate kidney function. In patients with CC less than 30 ml / min required to designate smaller doses trandolapril.
In patients with impaired renal function, chronic heart failure, bilateral renal artery stenosis or stenosis of the artery to a solitary kidney (eg, after transplantation) are at increased risk of deterioration of renal function. Some hypertensive patients, with no violations pocheh functions in the appointment of trandolapril in combination with a diuretic may experience increased blood urea nitrogen and serum creatinine.
Hyperkalemia
in patients with arterial hypertension, particularly with impaired renal function, Tarka medication can cause hyperkalemia.
Surgery / general anesthesia
during surgery or general anesthesia using drugs that cause hypotension, trandolapril can block the formation of angiotensin II, associated with compensatory renin release.
Desensitization
Patients receiving ACE inhibitors during the course of desensitization (eg, poison Hymenoptera), in rare cases may develop life-threatening anaphylactic reactions.
LDL-apheresis
During the LDL-apheresis in patients receiving ACE inhibitors, saw the development of life-threatening anaphylactic reactions.
Effects on ability to drive vehicles and use machines
Caution should be exercised when driving and occupation of other potentially hazardous activities that require high concentration and psychomotor speed reactions, especially at the beginning of treatment. The drug Tarka may enhance the blood alcohol content and slow down its excretion. In this regard, the effects of alcohol can be reinforced.
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 and P-glycoprotein. 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 table summarizes data on drug interactions due to the content of verapamil.
.
The following table summarizes the drug interaction caused verapamil.
Preparation Possible effect on verapamil or verapamil to another drug while applying
Alpha-blockers
Prazosin Increase in C max of prazosin (approximately 40%), no effect on T 1/2 prazosin.
Increased AUC terazosin terazosin (approximately 24%) and C max (approximately 25%).
Antiarrhythmics
Flecainide Minimal effect on flecainide plasma clearance (<10%); no effect on verapamil plasma clearance.
Quinidine, quinidine Reduced oral clearance (about 35%).
bronchodilator agents
Reduction of oral theophylline and systemic clearance (about 20%). Smokers - a decline of about 11%.
Anticonvulsants
carbamazepine, carbamazepine Increased AUC (approximately 46%) in patients with refractory partial epilepsy.
Antidepressants
Imipramine Increased AUC imipramine (about 15%) does not affect the level of active metabolite desipramine.
Hypoglycemic agents for oral
Glyburide increasing C max glyburide (approximately 28%), AUC (approximately 26%).
Antiinfectives
Clarithromycin may increase the level of verapamil.
Erythromycin may increase the level of verapamil.
Rifampicin Reduced AUC (approximately 97%), C max(approximately 94%), bioavailability (approximately 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 oral clearance increases Verapamil about 5 times.
Benzodiazepines and other anxiolytics
Buspirone increases AUC and the C max of buspirone in 3.4 times.
Midazolam increases AUC (about 3 times) and C max(approximately 2 fold) midazolam.
Beta-blockers
metoprolol increases AUC (about 32.5%) and C max (approximately 41%) of metoprolol in patients with angina pectoris.
Propranolol increases AUC (approximately 65%) and C max (approximately 94%) of propranolol in patients with angina pectoris.
Cardiac glycosides
Digitoxin Reduced total clearance (about 27%) and extrarenal clearance (about 29%) of digitoxin.
Digoxin: In healthy volunteers, increased the C max (approximately% 45-53), the C ss (approximately 42%) and AUC (approximately 52%) of digoxin. Reducing the dose of digoxin.
Blockers of histamine H 2 -receptors
Cimetidine increases AUC R- and S-verapamil (approximately 25% and 40%, respectively) with decreasing clearance R- and S-verapamil.
Immunosuppressants
Cyclosporin increases AUC, C ss , C max (approximately 45%) of cyclosporin.
Sirolimus may increase sirolimus levels.
Tacrolimus may increase tacrolimus levels.
Everolimus may increase the level of everolimus.
Lipid-lowering agents, HMG-CoA reductase inhibitor
atorvastatin may increase levels of atorvastatin, increasing the level of verapamil by approximately 42.8% in plasma.
Lovastatin may increase the level of lovastatin.
Simvastatin increases AUC (approximately 2.6 times) and C max(about 4.6 times) of simvastatin.
Serotonin receptor antagonists
almotriptan increases AUC (approximately 20%) and C max (approximately 24%) of almotriptan.
Uricosuric agents
sulphinpyrazone Increased verapamil oral clearance (about 3 times), reducing its bioavailability (approximately 60%).
Other

Grapefruit juice Increased AUC R- and S-verapamil (approximately 49% and 37%, respectively) and C max R- and S-verapamil (approximately 75% and 51% respectively). T 1/2 and renal clearance did not change.
St. John's wort Reduced AUC R- and S-verapamil (approximately 78% and 80%, respectively) with decreasing C max.
Other possible types of interaction between verapamil
While the use of 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).
With simultaneous use ofquinidine drug-enhanced hypotensive effect of Tarka. 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 some 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.
With simultaneous use of carbamazepine with drug Tarka increased carbamazepine plasma levels that may be associated with side effects typical of carbamazepine - diplopia, headache, ataxia or dizziness.
With simultaneous use of lithium with the drug Tarka increased neurotoxicity lithium.
With simultaneous use of rifampicin with drug Tarka may decrease the hypotensive effect of verapamil.
colchicineIt is a substrate for the isoenzyme CYP3A4 and P-glycoprotein. It is known that verapamil inhibits isoenzyme CYP3A and P- glycoprotein. Therefore, while the use of verapamil colchicine concentration in the blood can rise significantly. The combined use of drugs is contraindicated.
In patients with coronary artery disease in the appointment of verapamil after taking dantrolene cases of hyperkalemia and suppress myocardial function were noted. Joint use of drugs is contraindicated.
With simultaneous use of sulfinpirazona with drug Tarka may decrease the hypotensive effect of verapamil.
When applied simultaneously with the drug effect Tarka relaxants may increase.
With simultaneous application of acetylsalicylic acid as antiplatelet agents verapamil may increase bleeding tendency.
While the use of verapamil level of ethanol in the blood plasma increases.
The simultaneous use of verapamil may lead to increased serum levels of simvastatin / atorvastatin / lovastatin .
Patients receiving verapamil treatment inhibitors of HMG-CoA reductase(i.e., simvastatin / atorvastatin / 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.
Fluvastatin, pravastatin and rosuvastatin are not metabolized by the action of the isoenzyme CYP3A4, however their interactions with verapamil least likely.
Interactions caused trandolapril
diuretics or other antihypertensives drugs may enhance the hypotensive effect of trandolapril.
Potassium-sparing diuretics (spironolactone, amiloride, triamterene) or potassium supplements increase the risk of hyperkalemia, especially in patients with renal insufficiency. Trandolapril can reduce the loss of potassium in the combined use with thiazide diuretics.
The simultaneous use of trandolapril (such as ACE inhibitors and any) with hypoglycaemic drugs (insulin or oral gipoglikemiche

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