Formula: C24H34N2O5, chemical name: (2S,3aR,7aS)-1-[(S)-N-[(S)-1-carboxy-3-phenylpropyl]alanyl]hexahydro-2-indolinecarboxylic acid 1- ethyl ether.
Pharmacological group: organotropic agents/ cardiovascular drugs/ ACE inhibitors.
Pharmachologic effect: hypotensive, cardioprotective, vasodilating, natriuretic.
Pharmacological properties
Trandolapril is a prodrug, the ethyl ester of a non-sulfhydryl angiotensin-converting enzyme inhibitor. Trandolapril is rapidly absorbed and nonspecifically hydrolyzed to trandolaprilat, which is a pharmacologically active metabolite. Trandolapril binds tightly to and inhibits angiotensin-converting enzyme and inhibits the production of angiotensin II, which has a vasoconstrictor effect. There is also a decrease in the concentration of aldosterone, atrial natriuretic factor, and an increase in plasma renin activity and the concentration of angiotensin I. Thus, trandolapril modulates the renin-angiotensin-aldosterone system, which plays a major role in regulating circulating blood volume, blood pressure, and consistently has an antihypertensive effect. Trandolapril reduces total peripheral resistance blood vessels, systemic blood pressure and afterload on the myocardium. Trandolapril helps reduce vascular hypertrophy (aorta, femoral and mesenteric arteries). Trandolapril, by inhibiting the tissue renin-angiotensin system of the heart, prevents the development of left ventricular dilatation and myocardial hypertrophy or promotes their regression (has a cardioprotective effect). Trandolapril in reperfusion ischemic areas of the myocardium increases the concentration of phosphocreatinine. Trandolapril stabilizes bradykinin in the blood and tissues (degradation of bradykinin to inactive peptides is reduced), suppresses the formation of aldosterone in the adrenal glands, increases the activity of the kallikrein-kinin system, increases biological release active substances(atrial natriuretic factor, endothelial relaxing factor, prostaglandins E2 and I2), which have a vasodilatory and natriuretic effect and improve blood flow in the kidneys. Trandolapril reduces the formation of endothelin-1 and arginine vasopressin, which have vasoconstrictor properties. The hypotensive effect of trandolapril develops approximately 1 hour after administration, becomes maximum after 8–12 hours, and lasts up to 24–36 hours. The maximum inhibition of angiotensin-converting enzyme in the blood serum is recorded after 2 - 4 hours, and after 24 hours the enzyme activity remains 80% lower than the initial value. The activity of angiotensin-converting enzyme in the blood, heart, lungs, and kidneys normalizes within 7 days after discontinuation of treatment, and in the arterial wall it remains reduced for a long time. The high effectiveness of trandolapril is explained by the formation of trandolaprilat (diacidic metabolite), which is 2200 times more active than the original substance. In patients with post-infarction left ventricular dysfunction (with an ejection fraction of no more than 35%), after using a dose of 4 mg per day for 24 to 50 months, a decrease in mortality from cardiovascular diseases and overall mortality by 25% and 22%, risk of developing sudden death by 24%, severe heart failure by 29%. According to calculations, the expected life expectancy in this category of patients increases by approximately 15 months (27%). But a significant improvement in survival after myocardial infarction was recorded only in patients with initial blood pressure above 125/90 mmHg.
No signs of carcinogenicity were found in experiments on rats and mice when using doses of trandolapril up to 8 mg/kg per day and up to 25 mg/kg per day, respectively. Trandolapril does not have genotoxic or mutagenic properties.
At doses up to 100 mg/kg per day (1250 times the maximum recommended human dose), trandolapril does not adversely affect fertility in rats. When using trandolapril in monkeys at doses of 25 mg/kg per day, in rats - 1000 mg/kg per day, in rabbits - 0.8 mg/kg per day (312, 1250, 10 times higher than the maximum recommended dose for humans, respectively ) no teratogenic effects were detected. But it must be taken into account that the use of other angiotensin-converting enzyme inhibitors during pregnancy may cause an increase in neonatal and fetal mortality, and use in the 2nd and 3rd trimesters of pregnancy is accompanied by delayed skeletal ossification, a decrease in placental weight, the development of oligohydramnios (due to decreased renal function), and renal failure. insufficiency in the fetus, anuria, even death, contractures of the limbs, hypoplasia lung tissue, non-closure of the Botallov duct, craniofascial deformations, toxic effects on the mother’s body.
Trandolapril, when taken orally, is rapidly absorbed from the gastrointestinal tract. For trandolapril, the absolute bioavailability is 10% and for trandolaprilat - approximately 40 - 60%. Maximum concentration trandolapril is achieved after 1 hour, trandolaprilat - after 4 – 10 hours. The maximum concentration and the area under the concentration-time curve are independent of the time of food intake. Trandolapril is bound to plasma proteins by 80% and is independent of concentration; trandolaprilat, depending on concentration, is bound by 65% at a concentration of 1000 ng/ml and up to 94% at a concentration of 0.1 ng/ml. With repeated doses of 2 mg or more, equilibrium concentrations are achieved within 4 days. The volume of distribution of trandolapril is approximately 18 liters. Trandolapril in the mucous membrane gastrointestinal tract and the liver is hydrolyzed (subjected to deesterification) to form an active metabolite - trandolaprilat, which has pronounced lipophilicity, which causes a decrease in the activity of angiotensin-converting enzyme not only in the blood, but also in the kidneys, lungs, especially in the adrenal glands and heart. The concentration of trandolapril in the blood serum decreases rapidly, the half-life is 0.7 - 1.3 hours. Trandolaprilat is excreted in 2 or 3 phases: the half-life of alpha is 3.3 - 4.5 hours, the half-life of beta is 16 - 24 hours. The terminal half-life of trandolaprilat exceeds 100 hours (possibly reflecting elimination after dissociation from the membrane angiotensin-converting enzyme complex). The renal clearance of trandolaprilat varies from 0.15 l/h to 4 l/h depending on the dose. The drug is excreted from the body with urine (1/3) and bile (2/3). In small amounts (less than 0.5%), trandolapril is excreted unchanged through the kidneys.
The pharmacokinetic parameters of trandolapril do not depend on the patient's age. Serum concentrations of trandolapril increase in elderly patients. But the plasma concentration of trandolaprilat and its pharmacological activity in patients with arterial hypertension elderly and young ages comparable.
In cases of severe liver damage, the content of trandolapril in the blood serum is approximately 10 times higher than that in healthy people.
For renal failure at speed glomerular filtration less than 30 ml/min and during hemodialysis, plasma concentrations of trandolapril and trandolaprilat are approximately 2 times higher, and renal clearance is reduced by approximately 85%. It is necessary to adjust the initial and maintenance dose of the drug.
Indications
Arterial hypertension (as part of monotherapy and combination treatment), heart failure (adjuvant therapy), left ventricular dysfunction after myocardial infarction.
Method of administration of trandolapril and dose
Trandolapril is taken orally, regardless of meals, 2–4 mg per day in 1–2 divided doses; if necessary, increasing doses should be done at least after 2–4 weeks. Patients at risk are prescribed an initial dose of 1 mg per day; in case of violation functional state liver treatment begins with 0.5 mg in the morning, but not more than 2 mg per day; for hemodialysis, an initial dose of 0.5 mg is prescribed in the morning.
During treatment, it is necessary to control blood pressure, composition peripheral blood(before the start of treatment, the first 3 - 6 months of treatment and then at periodic intervals up to 1 year, especially in patients with increased risk development of neutropenia), plasma potassium levels, protein, creatinine, urea nitrogen, body weight, renal function, diet.
Therapy with trandolapril should be carried out under regular medical supervision.
Dose selection for patients with severe heart failure or malignant arterial hypertension should be carried out in a hospital setting.
Some patients receiving diuretics may experience an excessive decrease in blood pressure after trandolapril administration. In patients with uncomplicated arterial hypertension, the development of symptomatic arterial hypotension was observed when taking the first dose of trandolapril, as well as when it was increased. The risk of its development is higher in patients with hyponatremia and hypovolemia, which developed as a result of prolonged diuretic therapy, dialysis, and consumption restriction table salt, vomiting or diarrhea. To reduce the risk of symptomatic hypotension 7 days before the start of therapy, it is necessary to adjust water-electrolyte balance and discontinue ongoing antihypertensive treatment, including the prescription of diuretics (or significantly reduce their dose).
During therapy with angiotensin-converting enzyme inhibitors, cases of suppression of function have been described. bone marrow and agranulocytosis. The risk of developing neutropenia is dose-dependent, depending on clinical condition patient and is determined by the type of drug. These adverse reactions are more common in patients with impaired renal function, especially with diffuse diseases connective tissue. In such patients, regular monitoring of the number of leukocytes in the blood and the concentration of protein in the urine is recommended, especially in cases of impaired renal function and therapy with antimetabolites and glucocorticosteroids. These reactions are reversible and return to normal after cessation of treatment with an angiotensin-converting enzyme inhibitor.
Trandolapril can cause angioedema of the extremities, face, tongue, larynx, and vocal folds. Angioedema when using angiotensin-converting enzyme inhibitors is more common in patients Negroid race. During therapy with angiotensin-converting enzyme inhibitors, cases of the development of angioedema of the intestine have also been noted, which must be taken into account when abdominal pain develops while taking trandolapril. In patients with angioedema, it is necessary to immediately stop taking the drug and monitor the patient until the edema resolves. Angioedema located in the facial area usually resolves spontaneously. Swelling that extends not only to the face but also to the vocal folds can be life-threatening due to the risk of obstruction respiratory tract. In case of angioedema of the tongue, larynx, vocal folds, immediate subcutaneous administration of a solution of adrenaline (epinephrine) is required, as well as other therapeutic activities if necessary.
Angiotensin-converting enzyme inhibitors may be used before treatment for renovascular hypertension is initiated or in cases where such treatment will not be carried out. In patients with bilateral or unilateral stenosis renal arteries the risk of developing renal failure and severe arterial hypotension increases during therapy with angiotensin-converting enzyme inhibitors. Use of diuretics may increase the risk. Impaired renal function may be manifested by minor changes in plasma creatinine concentration, even in patients with unilateral renal artery stenosis. In such patients, therapy should begin in a hospital setting with small doses of trandolapril, followed by careful dose selection under close medical supervision. The use of diuretics should be discontinued. Plasma potassium concentrations and renal function should be monitored during the first weeks of treatment.
Patients with creatinine clearance less than 30 ml/min may require a dose reduction of trandolapril; The functional state of the kidneys must be carefully monitored. The risk of deterioration of renal function is increased in patients with chronic heart failure, impaired renal function, unilateral or bilateral renal artery stenosis, one functioning kidney or after a kidney transplant. In some patients with arterial hypertension who do not have renal pathology, when trandolapril is prescribed along with a diuretic, an increase in serum concentrations of creatinine and blood urea nitrogen may be observed. Proteinuria may also develop, especially in patients with impaired renal function or when taking relatively high doses of angiotensin-converting enzyme inhibitors.
During treatment, careful monitoring of patients with impaired liver function is necessary. If fulminant liver necrosis progresses and cholestatic jaundice develops, treatment should be discontinued.
There is information that the combined use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers or aliskiren increases the risk of arterial hypotension, decreased renal function (including acute renal failure), hyperkalemia. For this reason, dual blockade of the renin-angiotensin-aldosterone system by concomitant use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers or aliskiren is not recommended. If treatment by double blockade of the renin-angiotensin-aldosterone system is absolutely necessary, then it should be carried out only under the supervision of a specialist and with careful monitoring of the functional state of the kidneys, blood pressure, and electrolyte concentrations. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers should not be used together in patients with diabetic nephropathy.
In patients with arterial hypertension, especially with impaired renal function, trandolapril can cause hyperkalemia. Risk factors for the development of hyperkalemia include taking potassium-sparing diuretics, renal failure, concomitant use of drugs for the treatment of hypokalemia, left ventricular dysfunction after myocardial infarction, diabetes.
When using angiotensin-converting enzyme inhibitors, a dry, non-productive cough may occur, which disappears after discontinuation of treatment.
When conducting surgical interventions(including dental) caution is required, especially when using general anesthetics that have a hypotensive effect. Trandolapril can block the secondary formation of angiotensin II, which is associated with a compensatory release of renin.
Hyposensitizing treatment may increase the risk of anaphylactic reactions. When desensitizing the body to Hymenoptera venoms, patients receiving angiotensin-converting enzyme inhibitors may develop anaphylactic reactions (including life-threatening ones).
It is necessary to avoid hemofiltration, hemodialysis through high-performance polyacrylonitrile metaallyl sulfate membranes (for example, AN69) or low-density lipoprotein apheresis, as the development of anaphylactoid reactions or anaphylaxis (including life-threatening ones) is possible.
Alcohol consumption should be avoided during therapy.
Use trandolapril with caution for vehicle drivers and people whose professions involve increased concentration attention and speed of psychomotor reactions.
Contraindications for use
Hypersensitivity (including to other angiotensin-converting enzyme inhibitors), a history of angioedema when using angiotensin-converting enzyme inhibitors, hereditary (idiopathic) angioedema, aortic stenosis, mitral stenosis, left ventricular outflow tract obstruction, pregnancy, breastfeeding, age under 18 years (efficacy and safety have not been established), combined use with aliskiren and aliskiren-containing drugs in patients with diabetes mellitus and/or impaired renal function.
Restrictions on use
Impaired kidney and/or liver function, autoimmune diseases(scleroderma, systemic lupus erythematosus and other systemic collagenoses), hyperkalemia, symptomatic arterial hypotension, inhibition of bone marrow hematopoiesis, conditions in which a decrease in circulating blood volume is possible (including diarrhea, vomiting, a diet with limited fluid and/or sodium chloride, hemodialysis), dehydration body, coronary or cerebral circulation, artery stenosis single kidney, one or bilateral stenosis of the renal arteries, conditions after kidney transplantation, severe heart failure; hypertrophic cardiomyopathy; diabetes; hyponatremia, dry nonproductive cough, use in black patients, combined use with beta-blockers, dialysis procedures, simultaneous low-density lipoprotein apheresis, surgical interventions or general anesthesia using drugs that cause arterial hypotension, long-term therapy with diuretics, simultaneous desensitization of the body to Hymenoptera venoms, old age.
Use during pregnancy and breastfeeding
The use of trandolapril is contraindicated during pregnancy. During therapy with trandolapril, reliable methods of contraception must be used. If pregnancy occurs during treatment with the drug, it must be discontinued immediately and, if necessary, prescribed alternative therapy. There is no information about the teratogenic effects of angiotensin-converting enzyme inhibitors in the first trimester of pregnancy, but this possibility cannot be completely excluded. Women who are planning pregnancy should be prescribed antihypertensive drugs, for which the safety of use during pregnancy has been proven, except in cases where continued treatment with angiotensin-converting enzyme inhibitors is necessary. It is known that when using angiotensin-converting enzyme inhibitors in the second and third trimester of pregnancy, feto toxic effect(oligohydramnios, impaired renal function, delayed ossification of the skull bones) and toxic effects (arterial hypotension, renal failure, hyperkalemia) on the newborn child. When using trandolapril, starting from the second trimester of pregnancy, ultrasound assessment of the condition of the skull bones and fetal kidney function is recommended. Newborns whose mothers took angiotensin-converting enzyme inhibitors during pregnancy should be under medical supervision to exclude arterial hypotension.
During therapy with trandolapril, breastfeeding should be stopped. Data on the penetration of trandolapril into breast milk No. For this group of patients, it is preferable to prescribe drugs with a proven safety profile, especially when feeding premature and newborn babies.
Side effects of trandolapril
Cardiovascular system and blood (hematopoiesis, hemostasis): a sharp decline blood pressure (especially during diuretic therapy, in patients with impaired water-salt metabolism), rush of blood to the skin of the face, orthostatic hypotension, angiopathy, arterial hypertension, palpitations, pain in chest, bradycardia, tachycardia, angina pectoris, arrhythmia, myocardial infarction, myocardial ischemia, ventricular tachycardia, heart failure, atrioventricular block, cardiac arrest, varicose veins veins, peripheral vascular disorders, decreased hematocrit, hemoglobin level, neutropenia, platelet disorders, leukocyte disorders, leukopenia, agranulocytosis, anemia (including hemolytic), thrombocytopenia, erythrocytopenia, pancytopenia, eosinophilia.
Nervous system and sensory organs: headache, dizziness, fainting, sleep disturbance, insomnia, asthenia, migraine, drowsiness, feeling tired, hallucinations, agitation, anxiety, apathy, dynamic disturbances cerebrovascular accident, lethargy, confusion, imbalance, depression, paresthesia, cerebral stroke, seizures, transient ischemic attack, cerebral hemorrhage, taste disturbance, loss of taste, blurred vision, blurred vision visual perception, blepharitis, eye diseases, swelling of the mucous membrane of the eye, blurred vision, vertigo, tinnitus.
Respiratory system: dyspnea, rhinitis, cough, bronchospasm, sinusitis, bronchitis, pharyngitis, upper respiratory tract congestion, upper respiratory tract inflammation, upper and lower respiratory tract infections, pain in the oropharynx, nose bleed, breathing disorders.
Digestive system: dry mouth, glossitis, dyspepsia, nausea, diarrhea, vomiting (including blood), constipation, liver dysfunction, anorexia, gastrointestinal pain, gastrointestinal disorders, increased appetite, gastritis, flatulence, decreased appetite, cholestatic jaundice , abdominal pain, fulminant liver necrosis with fatal outcome, pancreatitis, hepatitis, intestinal obstruction, angioedema of the intestine,
Skin: psoriatic skin changes, skin allergic reactions, rash, itchy skin, photosensitivity, bullous pemphigus, alopecia, onycholysis, hyperhidrosis, angioedema, eczema, acne, dry skin, skin diseases, dermatitis, erythema multiforme, Stevens-Johnson syndrome, psoriasis, psoriasis-like dermatitis, epidermal necrolysis, urticaria.
Support and movement system: myalgia, arthritis, arthralgia, cramps, muscle spasms, back pain, limb pain, osteoarthritis, bone pain.
Genitourinary system: renal dysfunction, proteinuria, renal failure, infections urinary tract, edema, impotence, decreased libido, pollakiuria, polyuria, azotemia, erectile dysfunction.
Others: congenital arterial malformation, ichthyosis, enzymatic dysfunction, chest pain, peripheral edema, weakness, poor health, edema, increased fatigue, angioedema, development of infections, fever, abnormal electrocardiogram readings, hypersensitivity reactions, gout, trauma, hyperglycemia, hyperkalemia, uratemia, hypercholesterolemia, hyperuricemia, hyperlipidemia, hyponatremia, hyperproteinemia, increased concentrations of bilirubin, creatinine and liver enzymes in the blood plasma, increased activity of gammaglutamyltransferase, increased immunoglobulin levels, increased activity of lactate dehydrogenase, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, increased lipase activity.
Interaction of trandolapril with other substances
The effect of trandolapril is mutually enhanced (additive effect) by other antihypertensive drugs, including methyldopa, terazosin, risperidone, diuretics, nitrates, calcium channel blockers, beta-blockers (including with significant systemic absorption from ophthalmic dosage forms), alcohol.
Beta blockers should only be used with trandolapril under close medical supervision.
The combined use of trandolapril with hypoglycemic drugs (insulin, oral hypoglycemic agents) may enhance the hypoglycemic effect and increase the risk of hypoglycemia.
Data from clinical studies have shown that dual blockade of the renin-angiotensin-aldosterone system through the combined use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers or aliskiren is associated with more high frequency development adverse reactions such as hyperkalemia, arterial hypotension, decreased renal function (including acute renal failure) compared with the use of one medicinal product, affecting the renin-angiotensin-aldosterone system.
The effect of trandolapril is weakened by sympathomimetics, non-steroidal anti-inflammatory drugs ( acetylsalicylic acid, ibuprofen, ketorolac, meloxicam, naproxen, piroxicam and others), estrogens, drugs that activate the renin-angiotensin-aldosterone system.
With the simultaneous use of angiotensin-converting enzyme inhibitors and gold preparations (sodium aurothiomalate), nitrate-like reactions (nausea, flushing of the face, vomiting, marked decrease in blood pressure) were observed.
Trandolapril may enhance the antihypertensive effect of some inhalational anesthesia drugs.
Cyclosporine, potassium-sparing diuretics (amiloride, spironolactone, triamterene and others), potassium supplements, salt substitutes and other potassium-containing drugs for joint use with trandolapril increase the risk of developing hyperkalemia.
Myelosuppressants increase the risk of developing fatal neutropenia or/agranulocytosis when used together with trandolapril.
Procainamide and allopurinol, when used together with trandolapril, increase the risk of developing neutropenia.
Antacids may reduce the bioavailability of trandolapril.
Trandolapril reduces diuretic-induced hypokalemia and signs of hyperaldosteronism, enhances the inhibitory effect of alcohol on the central nervous system. nervous system, increases the toxic effect (due to increased concentration) of lithium.
When trandolapril is used together with tricyclic antidepressants and antipsychotics, the risk of developing orthostatic hypotension increases.
When trandolapril is used together with non-steroidal anti-inflammatory drugs, the risk of developing renal dysfunction increases.
Anaphylactoid reactions have been described when high-flux polyacrylonitrile membranes were used during hemodialysis in patients receiving angiotensin-converting enzyme inhibitors. The use of such membranes should be avoided when prescribing angiotensin-converting enzyme inhibitors to patients on dialysis.
Overdose
In case of an overdose of trandolapril, acute arterial hypotension, stupor, shock, bradycardia, renal failure, fluid and electrolyte disturbances, and angioedema develop.
Treatment: complete withdrawal or reduction of the dose of the drug; washing the stomach and intestines, transferring the patient to a horizontal position, carefully monitoring blood pressure, taking measures to increase the volume of circulating blood (introducing saline solution and other blood-substituting fluids), supporting and symptomatic treatment: epinephrine (intravenous or subcutaneous), hydrocortisone (intravenous), antihistamines. A specific antidote for trandolapril is unknown. There is no information on the possibility of removing trandolapril or trandolaprilat by hemodialysis.
pharmachologic effect
Tarka - combination drug, which contains long-acting verapamil and trandolapril.
Trandolapril is the ethyl ester (prodrug) of the non-sulfhydryl ACE inhibitor trandolaprilat.
Verapamil hydrochloride is a slow calcium channel blocker (SCBC).
Trandolapril
Trandolapril suppresses the activity of the renin-angiotensin-aldosterone system in the 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-active decapeptide). The latter turns into action of ACE(peptidyl dipeptidases) into angiotensin II is a powerful vasoconstrictor that causes constriction of the arteries and an increase in blood pressure, and also stimulates the secretion of aldosterone by the adrenal glands.
ACE inhibition leads to a decrease in the concentration of angiotensin II in the blood plasma, which is accompanied by a decrease in vasopressor activity and aldosterone secretion. Although aldosterone production decreases slightly, it can nevertheless be observed slight increase serum potassium concentrations combined with sodium and water loss.
Reduction in angiotensin II concentration by mechanism feedback leads to an increase in renin activity in the blood plasma. Another function of ACE is the destruction of kinins (bradykinin), which have powerful vasodilatory properties, into inactive metabolites. In this regard, the suppression of ACE leads to an increase in circulating and tissue concentrations of the kallikrein-kinin system, which promotes vasodilation through activation of the prostaglandin system. This mechanism may partly account for the hypotensive effect 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 the glomerular filtration rate usually does not change. Abrupt cessation therapy was not accompanied by a rapid increase in blood pressure.
The antihypertensive effect of trandolapril appears 1 hour after oral administration and persists for up to at least, 24 hours. In some cases, optimal blood pressure control can be achieved only a few weeks after the start of treatment. At long-term therapy the hypotensive effect remains. Trandolapril does not worsen the circadian blood pressure profile.
Verapamil
Verapamil inhibits the flow of calcium ions through the "slow" calcium channel membranes of vascular smooth muscle cells, conductive and contractile cardiomyocytes. Verapamil causes a decrease in blood pressure, both at rest and during physical activity due to the expansion of peripheral arterioles. As a result of a decrease in peripheral vascular resistance (afterload), the myocardial oxygen demand and energy consumption are reduced. Verapamil reduces myocardial contractility. The negative inotropic effect of the drug can be compensated by a decrease in peripheral vascular resistance. The cardiac index does not decrease, except for patients with left ventricular dysfunction.
Verapamil does not affect the sympathetic regulation of cardiac activity because it does not block β-adrenergic receptors. bronchial asthma and bronchospastic conditions are not a contraindication to the use of veralamil.
Tarka
In studies in healthy volunteers, there was no evidence of interaction between verapamil and trandolapril at the level of pharmacokinetic parameters or the RAAS. Therefore, the synergy of the two medicines reflects their complementary pharmacodynamic effects. IN clinical studies Tarka lowered blood pressure to a greater extent than both drugs alone.
Pharmacokinetics
Trandolapril
Suction
After oral administration, trandolapril is rapidly absorbed. Absolute bioavailability is about 10%. TC max in blood plasma is about 1 hour.
Distribution
The binding of trandolapril to plasma proteins is about 80% and is independent of concentration. V d of trandolapril is about 18 liters. T 1/2<1 ч. При многократном применении C ss достигается примерно через 4 дня, как у здоровых добровольцев, так и у пациентов молодого и пожилого возраста с артериальной гипертензией.
Metabolism
In blood plasma, trandolapril undergoes hydrolysis to form the active metabolite trandolaprilat. TC max of trandolaprilat in blood plasma is 3-8 hours. C max and AUC do not depend on food intake. The absolute bioavailability of trandolaprilat when taking trandolapril is about 13%. The binding to blood proteins depends on the concentration and varies from 65% (at a concentration of 1000 ng/ml) to 94% (at a concentration of 0.1 ng/ml). At steady state, the concentration of the effective half-life 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.
Removal
Trandolaprilat has a high affinity for ACE. 9-14% of the trandolapril dose is excreted as trandolaprilat by the kidneys. After taking labeled trandolapril orally, 33% of the drug was excreted by the kidneys and 66% through the intestines. A small amount is excreted unchanged through the kidneys (less than 0.5%).
The renal clearance of trandolaprilat varies from 0.15 to 4 l/h depending on the dose.
Children. The pharmacokinetics of trandolapril have not been studied in children under 18 years of age.
Elderly patients. Plasma concentrations of trandolapril increase in elderly patients with arterial hypertension (over 65 years of age). However, the plasma concentration of trandolaprilat and its ACE-inhibitory activity in elderly and young patients with arterial hypertension are the same. The pharmacokinetics of trandolapril and trandolaprilat, as well as ACE-inhibiting activity in elderly patients of both sexes are the same.
Kidney failure. Compared with healthy volunteers in patients on hemodialysis and with CC<30 мл/мин плазменная концентрация трандолаприлата примерно в 2 раза выше, а почечный клиренс снижен приблизительно на 85%. Пациентам с почечной недостаточностью рекомендована коррекция дозы препарата.
Liver failure. Compared with healthy volunteers, in patients with alcoholic cirrhosis, the plasma concentrations of trandolapril and trandolaprilat increase by 9 and 2 times, respectively, but the ACE inhibitory activity does not change. In patients with liver failure, lower doses of the drug may be required.
Verapamil
Suction
About 90% of an oral dose of verapamil is rapidly absorbed in the small intestine. Bioavailability is only 22% due to the pronounced “first pass” effect through the liver. With repeated use, the average bioavailability can increase up to 30%. Food intake does not affect the bioavailability of the drug. TC max is 4-15 hours. The maximum plasma concentration of norverapamil is achieved approximately 5-15 hours after taking the drug.
Distribution
C ss with repeated use 1 time/day is achieved after 3-4 days. The binding to plasma proteins is about 90%.
Metabolism
One of the 12 metabolites found in urine is norverapamil, the pharmacological activity of which is 10-20% of that of verapamil; its share is 6% of the excreted drug. The C ss of norverapamil and verapamil are similar.
Removal
T1/2 with repeated use is an average of 8 hours. 3-4% of the dose is excreted unchanged by the kidneys. Metabolites are excreted by the kidneys (70%) and through the intestines (16%).
Pharmacokinetics in special clinical situations
The pharmacokinetics of verapamil does not change with impaired renal function. Impaired renal function does not affect the elimination of verapamil.
The bioavailability and half-life of verapamil are increased in patients with liver cirrhosis. 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/trandolaprilat, therefore the pharmacokinetics of both drugs when used in combination do not differ from that when they are prescribed separately.
Indications
- essential arterial hypertension (in patients for whom combination therapy is indicated).
Dosage regimen
For adults Prescribe 1 caps. 1 time/day The drug should be taken orally, preferably in the morning after meals. The capsule is swallowed whole with water.
Side effect
The following are side effects that had a possible or probable connection with the drug: Tarka during clinical trials.
often (from ≥1/100 to<1/10): головная боль, головокружение.
often (from ≥1/100 to<1/10): AV-блокада I степени.
(from ≥1/100 to<1/10): кашель.
Gastrointestinal disorders:(from ≥1/100 to<1/10): запор.
Common disorders: often (from ≥1/100 to<1/10): астения.
In addition to the reactions identified during clinical trials, the following side effects were identified during post-registration use:
Infectious diseases: bronchitis.
leukopenia, thrombocytopenia.
Metabolic disorders: hyperkalemia.
Mental disorders: anxiety, insomnia.
Nervous system disorders: imbalance, paresthesia, drowsiness, fainting.
Visual disorders: blurred vision, “veil” before the eyes.
Labyrinthviolations: dizziness.
Cardiovascular system disorders: complete AV block, resting angina, bradycardia, sensation
palpitations, tachycardia.
arterial hypotension, hyperemia of the skin, flushes of blood to the facial skin.
Disorders of the respiratory system, chest and mediastinal organs: shortness of breath, nasal congestion.
Gastrointestinal disorders: nausea, diarrhea, dry mouth.
Stevens-Johnson syndrome, angioedema, itching, rash.
Musculoskeletal and connective tissue disorders: arthralgia, myalgia.
pollakiuria, polyuria.
Genital disorders: erectile disfunction.
Common disorders: chest pain, swelling, weakness.
increased LDH activity, alkaline phosphatase activity, creatinine concentration, urea concentration, ALT, AST blood activity.
verapamil:
hypersensitivity.
Endocrine system disorders: hyperprolactinemia.
Cardiac disorders: AV blockade I, II, III degrees, sinus node arrest (“sinus arrest”), heart failure.
gum hyperplasia, abdominal pain, abdominal discomfort.
Disorders of the skin and subcutaneous tissues: hives.
Breast disorders: gynecomastia, galactorrhea.
There are several individual reports of cases of paralysis (tetraparesis) associated with the combined use of
verapamil and colchicine. This could be due to the penetration of colchicine through the BBB due to the suppression of the activity of the enzyme CYP 3A4 and P-glycoprotein under the influence of verapamil. The combined use of colchicine and verapamil is not recommended.
Additional significant side effects observed with use trandolapril:
Blood and lymphatic system disorders: agranulocytosis.
Immune system disorders: hypersensitivity.
Gastrointestinal disorders: vomiting, abdominal pain, pancreatitis.
Disorders of the skin and subcutaneous tissues: alopecia.
Common disorders: fever.
The following are side effects that have been reported with use: other ACE inhibitors:
Blood and lymphatic system disorders: pancytopenia.
Nervous system disorders: transient cerebrovascular accident.
Cardiac disorders: myocardial infarction, cardiac arrest.
Vascular disorders: cerebral hemorrhage.
Digestive system disorders: intestinal angioedema.
Disorders of the skin and subcutaneous tissues: erythema multiforme, toxic epidermal necrolysis.
Renal and urinary tract disorders: acute renal failure.
Laboratory and instrumental data: decrease in hemoglobin and hematocrit.
Contraindications for use
- history of angioedema associated with taking ACE inhibitors;
- hereditary and idiopathic Quincke's edema;
- cardiogenic shock;
— chronic heart failure of functional class III and IV according to the NYHA classification;
- AV blockade of the II and III degrees (except for patients with an artificial pacemaker);
- sinoatrial block;
- acute myocardial infarction;
— SSSU (except for patients with an artificial pacemaker);
- acute heart failure;
— atrial fibrillation/flutter in patients with Wolff-Parkinson-White syndrome;
- severe bradycardia;
- severe arterial hypotension;
- severe renal impairment (KR)<30 мл/мин);
- pregnancy;
- period of breastfeeding;
- age under 18 years (efficacy and safety have not been established);
- simultaneous use with colchicine and dantrolene;
- aortic stenosis or obstruction of the left ventricular outflow tract;
— hypertrophic obstructive cardiomyopathy;
- simultaneous use with beta-blockers (iv) (for
excluding patients undergoing treatment in the intensive care unit);
- lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome (the drug contains lactose);
- hypersensitivity to any component of the drug or to any other ACE inhibitor.
WITH caution: hyperkalemia; disrupting liver function
and/or renal function (creatinine clearance more than 30 ml/min); with systemic
connective tissue diseases (including systemic lupus erythematosus, scleroderma), especially during treatment
corticosteroids and antimetabolites; risk of developing agranulocytosis and neutropenia; inhibition of bone marrow hematopoiesis, AV block of the first degree; bradycardia; arterial hypotension; conditions accompanied by a decrease in blood volume (including diarrhea, 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, syndrome Lambert-Eaton, severe Duchenne muscular dystrophy); in patients on a diet with limited salt; before the low-density lipoprotein (LDL) apheresis procedure, simultaneous
carrying out desensitizing therapy with allergens (for example, hymenoptera venom) - the risk of developing anaphylactoid reactions (in some cases, life-threatening); surgical intervention (general anesthesia) - risk of developing excessive
lowering blood pressure, hemodialysis using high-flow polyacrylonitrile membranes - the risk of developing anaphylactoid
reactions.
Use during pregnancy and breastfeeding
Pregnancy
The safety of using Tarka in pregnant women has not been established. Use during pregnancy is contraindicated.
There are isolated observations of the development of pulmonary hypoplasia in newborns, intrauterine growth retardation, patent ductus arteriosus and hypoplasia of the skull bones after the use of ACE inhibitors during
pregnancy.
There is no information about the teratogenic or embryo/fetotoxic effects of ACE inhibitors in the first trimester of pregnancy, but this possibility cannot be completely excluded. In patients planning a pregnancy, antihypertensive drugs that have been proven safe for use during pregnancy should be prescribed, unless the use of ACE inhibitors is necessary. If pregnancy occurs while taking an ACE inhibitor, it should be discontinued immediately and more appropriate treatment prescribed.
It is known that when using ACE inhibitors in the second and third trimester of pregnancy, fetotoxicity is possible.
the effect of drugs (impaired renal function, oligohydramnios, delayed ossification of the skull bones) and toxic effects on the newborn (renal failure, arterial hypotension, hyperkalemia). In the case of trandolapril use, starting from the second trimester of pregnancy, ultrasound assessment of fetal kidney function and the condition of the skull is recommended. Newborns whose mothers took ACE inhibitors during pregnancy should be under medical supervision to exclude arterial hypotension.
Breastfeeding period
The use of Tarka during breastfeeding is contraindicated. Verapamil is excreted into breast milk.
There are no data on the use of trandolapril during breastfeeding. Preference should be given to drugs with a studied safety profile for this group of patients, especially when feeding newborns and premature infants.
Use in children
Contraindicated in children and adolescents under 18 years of age.
Overdose
In clinical studies, the maximum dose of trandolapril was 16 mg. However, there were no signs of intolerance.
symptoms caused by verapamil: marked decrease in blood pressure, AV block, bradycardia, asystole. Overdose deaths have been reported.
In case of an overdose of Tarka, the following are possible: symptoms caused by trandolapril: marked decrease in blood pressure, shock, stupor, bradycardia, electrolyte disturbances, renal failure.
Treatment: symptomatic. Treatment of verapamil overdose includes parenteral administration of calcium supplements, the use of beta-agonists and gastric lavage. Given the slow absorption of the long-acting drug, the patient's condition should be monitored for 48 hours; Hospitalization may be required during this period. Verapamil is not removed by hemodialysis.
Drug interactions
Interactions due to verapamil
In vitro studies indicate that verapamil is metabolized by the isoenzymes CYP3A4, CYP1A2, CYP2C8, CYP2C9 and CYP2C18.
Verapamil is an inhibitor of CYP3A4 and P-glycoprotein. A clinically significant interaction was observed when used concomitantly with CYP3A4 inhibitors, with an increase in verapamil plasma levels observed, while CYP3A4 inducers decreased verapamil plasma concentrations. Accordingly, when using such agents simultaneously, the possibility of this interaction should be taken into account.
The table summarizes the data on drug interactions caused by verapamil content.
The table summarizes the data on drug interactions caused by verapamil.
| A drug | Possible effect on verapamil or verapamil on another drug when used simultaneously |
| Alpha blockers | |
| Prazosin | An increase in Cmax of prazosin (approximately 40%) does not affect T1/2 of prazosin. |
| Terazosin | Increased terazosin AUC (approximately 24%) and Cmax (approximately 25%). |
| Antiarrhythmic drugs | |
| Flecainide | Minimal effect on plasma clearance of flecainide (<10%); не влияет на плазменный клиренс верапамила. |
| Quinidine | Reduced oral clearance of quinidine (approximately 35%). |
| Bronchodilators | |
| Theophylline | Decreased oral and systemic clearance (approximately 20%). For smokers - a decrease of approximately 11%. |
| Anticonvulsants | |
| Carbamazepine | Increased AUC of carbamazepine (approximately 46%) in patients with intractable partial epilepsy. |
| Antidepressants | |
| Imipramine | An increase in the AUC of imipramine (approximately 15%) does not affect the level of the active metabolite, desipramine. |
| Hypoglycemic agents for oral administration | |
| Glyburide | Glyburide Cmax increases (approximately 28%), AUC (approximately 26%). |
| Antimicrobials | |
| Clarithromycin | |
| Erythromycin | Verapamil levels may increase. |
| Rifampicin | The AUC (approximately 97%), Cmax (approximately 94%), bioavailability (approximately 92%) of verapamil decreases. |
| Telithromycin | Verapamil levels may increase. |
| Antitumor agents | |
| Doxorubicin | The AUC (89%) and Cmax (61%) of doxorubicin increases when verapamil is taken orally in patients with small cell lung cancer. The administration of verapamil intravenously in patients with progressive neoplasms does not affect the plasma clearance of doxirubicin. |
| Barbiturates | |
| Phenobarbital | The oral clearance of verapamil increases approximately 5-fold. |
| Benzodiazepines and other tranquilizers | |
| Buspirone | The AUC and Cmax of buspirone increases by 3.4 times. |
| Midazolam | The AUC (about 3 times) and Cmax (about 2 times) of midazolam increases. |
| Beta blockers | |
| Metoprolol | The AUC (approximately 32.5%) and Cmax (approximately 41%) of metoprolol increases in patients with angina pectoris. |
| Propranolol | The AUC (approximately 65%) and Cmax (approximately 94%) of propranolol increases in patients with angina pectoris. |
| Cardiac glycosides | |
| Digitoxin | The total clearance (approximately 27%) and extrarenal clearance (approximately 29%) of digitoxin decreases. |
| Digoxin | In healthy volunteers, C max (by approximately 45-53%), C ss (by approximately 42%), and AUC (by approximately 52%) of digoxin increase. Reducing the dose of digoxin. |
| Histamine H2 receptor blockers | |
| Cimetidine | The AUC of R- and S-verapamil increases (approximately 25% and 40%, respectively) with a decrease in the clearance of R- and S-verapamil. |
| Immunosuppressants | |
| Cyclosporine | AUC, C ss, C max increases (by approximately 45%) of cyclosporine. |
| Sirolimus | There may be an increase in sirolimus levels. |
| Tacrolimus | Tacrolimus levels may increase. |
| Everolimus | Everolimus levels may increase. |
| Lipid-lowering drugs-HMG-CoA reductase inhibitors | |
| Atorvastatin | There may be an increase in the level of atorvastatin, an increase in the level of verapamil by approximately 42.8% in the blood plasma. |
| Lovastatin | Possible increase in lovastatin levels. |
| Simvastatin | The AUC (about 2.6 times) and Cmax (about 4.6 times) of simvastatin increases. |
| Serotonin receptor antagonists | |
| Almotriptan | The AUC (approximately 20%) and Cmax (approximately 24%) of almotriptan increases. |
| Uricosuric drugs | |
| Sulfinpyrazone | An increase in the oral clearance of verapamil (approximately 3 times), a decrease in its bioavailability (approximately 60%). |
| Other | |
| Grapefruit juice | Increased AUC of R- and S-verapamil (approximately 49% and 37%, respectively) and Cmax of R- and S-verapamil (approximately 75% and 51%, respectively). T1/2 and renal clearance did not change. |
| St. John's wort | The AUC of R- and S-verapamil decreases (approximately 78% and 80%, respectively) with a decrease in C max. |
Other possible interactions with verapamil
antiarrhythmic drugs and beta-blockers an increased adverse effect on the cardiovascular system is possible (more pronounced AV blockade, a more significant decrease in heart rate, the development of heart failure and increased arterial hypotension).
When used simultaneously quinidine with the drug Tarka, the hypotensive effect is enhanced. Patients with hypertrophic obstructive cardiomyopathy may develop pulmonary edema.
When used simultaneously antihypertensives, diuretics and vasodilators with the drug Tarka, the hypotensive effect is enhanced.
When used simultaneously with Tarka prazosin, terazosin the hypotensive effect is enhanced.
When used concomitantly with Tarka, some drugs for the treatment of HIV infection (ritonavir), can inhibit the metabolism of verapamil, which leads to an increase in its concentration in the blood plasma. When used concomitantly, the dose of verapamil should be reduced.
When used simultaneously carbamazepine with Tarka, the level of carbamazepine in the blood plasma increases, which may be accompanied by side effects characteristic of carbamazepine - diplopia, headache, ataxia or dizziness.
When used simultaneously lithium with the drug Tarka, the neurotoxicity of lithium increases.
When used simultaneously rifampicin
Colchicine is a substrate for the CYP3A4 isoenzyme and P-glycoprotein. It is known that verapamil suppresses the activity of the CYP3A isoenzyme and P-glycoprotein. Therefore, when used simultaneously with verapamil, the concentration of colchicine in the blood may increase significantly. The combined use of drugs is contraindicated.
In patients with coronary artery disease when prescribing verapamil after taking dantrolene Cases of hyperkalemia and suppression of myocardial function have been reported. The combined use of drugs is contraindicated.
When used simultaneously sulfinpyrazone with Tarka it is possible to reduce the hypotensive effect of verapamil.
When used simultaneously with the drug Tarka, the effect muscle relaxants may intensify.
When used simultaneously acetylsalicylic acid as an antiplatelet agent with verapamil, the tendency to bleeding may increase.
When used simultaneously with verapamil, the level ethanol in blood plasma increases.
Concomitant use with verapamil may lead to an increase in serum levels. simvastatin/atorvastatin/lovastatin.
For patients receiving verapamil, treatment HMG-CoA reductase inhibitors(i.e. simvastatin/atorvastatin/lovastatin) should be started with the lowest possible doses and gradually increased during therapy. If it is necessary to prescribe verapamil to patients already receiving HMG-CoA reductase inhibitors, then their doses should be reconsidered and reduced according 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.
Interactions due to trandolapril
Diuretics or other antihypertensive 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 failure. Trandolapril may reduce potassium loss when used concomitantly with thiazide diuretics.
Concomitant use of trandolapril (as with any ACE inhibitors) with hypoglycemic agents (insulin or oral hypoglycemic agents) may enhance the hypoglycemic effect and lead to an increased risk of hypoglycemia.
Trandolapril may impair excretion lithium. Monitoring of serum lithium levels is necessary.
Other interactions
Anaphylactoid reactions have been described when high-flux polyacrylonitrile membranes were used during hemodialysis in patients receiving ACE inhibitors. In patients receiving ACE inhibitors, the use of membranes of this type should be avoided during hemodialysis.
Nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce the hypotensive effect of trandolapril, therefore, when adding NSAIDs to trandolapril therapy or their withdrawal, blood pressure control is necessary.
ACE inhibitors may enhance the hypotensive effect of some inhalational anesthetics.
Allopuripol, cytostatics, immunosuppressive agents and systemic corticosteroids or procainamide may increase the risk of leukopenia when treated with ACE inhibitors.
Antiacids may reduce the bioavailability of ACE inhibitors.
The antihypertensive effect of ACE inhibitors may be reduced when sympathomimetics are co-administered. In such cases, careful monitoring is necessary.
As with the use of any other antihypertensive drugs, co-administration of antipsychotics or tricyclic antidepressants increases the risk of developing orthostatic hypotension.
Conditions for dispensing from pharmacies
The drug is available with a prescription.
Storage conditions and periods
At a temperature not exceeding 25°C. Keep out of the reach of children. Shelf life - 3 years.
Use for liver dysfunction
The drug should be prescribed with caution to patients with impaired liver function.
Use for renal impairment
The use of the drug is contraindicated in case of severe renal impairment (KR<30 мл/мин.).
Carefully The drug should be used for bilateral renal artery stenosis, stenosis of the artery of a single kidney, and the condition after kidney transplantation.
special instructions
Liver dysfunction
Since trandolapril is metabolized in the liver to form an active metabolite, patients with impaired liver function should use the drug with caution and with careful medical supervision.
Arterial hypotension
In patients with uncomplicated arterial hypertension, after taking the first dose of trandolapril or increasing the dose of the drug, the development of arterial hypotension, accompanied by clinical symptoms, was noted. The risk of arterial hypotension is higher when water and electrolyte balance is disturbed as a result of long-term diuretic therapy, salt restriction, dialysis, diarrhea or vomiting. In such patients, before initiating trandolapril therapy, diuretic therapy should be discontinued and blood volume and/or sodium levels should be replaced.
Agranulocytosis/suppression of bone marrow hematopoiesis
During treatment with ACE inhibitors, cases of agranulocytosis and suppression of bone marrow function have been described. These phenomena are more often
occur in patients with impaired renal function, especially with systemic connective tissue diseases. U
It is advisable to regularly monitor such patients (for example, with systemic lupus erythematosus or scleroderma)
the number of leukocytes 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.
During treatment with ACE inhibitors, cases of angioedema of the intestine have also been reported. 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 combination drug should be avoided in patients with severe left ventricular dysfunction (for example, with a ventricular ejection fraction of less than 30%, an increase in pulmonary capillary wedge 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 are receiving beta-blockers.
Special patient groups
Tarka has not been studied in children under 18 years of age and is therefore not recommended for use in this age group.
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.
Renal dysfunction
When examining patients with arterial hypertension, renal function should always be assessed. In patients with CC less than 30 ml/min, lower doses of trandolapril are required.
Patients with impaired renal function, chronic heart failure, bilateral renal artery stenosis, or arterial stenosis of a solitary kidney (for example, after kidney transplantation) have an increased risk of deterioration in renal function. In some patients with arterial hypertension, without impaired kidney function, when trandolapril is prescribed in combination with a diuretic, an increase in blood urea nitrogen and serum creatinine may be observed.
Hyperkalemia
In patients with arterial hypertension, especially those with impaired renal function, Tarka may cause hyperkalemia.
Surgery/general anesthesia
During surgical interventions or general anesthesia with the use of drugs that cause arterial hypotension, trandolapril can block the formation of angiotensin II associated with the compensatory release of renin.
Desensitization
In patients receiving ACE inhibitors during a course of desensitization (for example, hymenoptera venom), in rare cases, life-threatening anaphylactic reactions may develop.
LDL apheresis
When performing LDL apheresis in patients receiving ACE inhibitors, the development of life-threatening anaphylactic reactions was observed.
Impact on the ability to drive vehicles and operate machinery
Care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions, especially at the beginning of treatment. Tarka may increase blood alcohol levels and slow down alcohol elimination. Due to this, the effects of alcohol may be enhanced.
The drug "Trandolapril" has a hypotensive effect and is widely used to treat arterial hypertension. It can be used both as a single medication and in combination treatment. Before starting use, you should carefully read the instructions for use of the medicine.
Composition and release form
Trandolapril is available in the form of red gelatin capsules. One capsule contains 2 milligrams of the active ingredient trandolapril. Additional substances are povidone, sodium stearyl, corn starch and lactose monohydrate. Capsules are located on blisters, which are packaged in cardboard packaging.
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Mechanism of action
The effect of stabilizing pressure lasts the whole day. According to the instructions for use, the drug allows you to reduce the accumulation of angiotensin 2, aldosterone and increase plasma renin activity and the concentration of angiotensin 1. Due to this, modulation of the RAAS occurs, which is responsible for the volume of circulating blood, and blood pressure levels drop. The antihypertensive effect is observed one hour after application. The maximum effect is achieved after 12 hours and continues throughout the day.
Indications for use
The instructions for use indicate that Trandolapril is prescribed for the treatment of the following diseases:
- arterial hypertension;
- heart failure.
Instructions for use of "Trandolapril"
The instructions for use indicate that Trandolapril is used according to the following scheme indicated in the table:
Contraindications
Instructions for use prohibit taking Trandolapril under the following conditions:
- Quincke's edema, which developed due to the use of ACE inhibitors;
- genetic predisposition to angioedema;
- aortic stenosis;
- pregnancy period;
- lactation;
- age under 18 years;
- individual intolerance to certain substances.
Side effects
The instructions for use indicate that Trandolapril sometimes causes the following side symptoms:
| Areas of possible impact | Phenomena |
| Blood-forming organs |
|
| Skin |
|
| Respiratory system |
|
| Gastrointestinal tract |
|
| Urinary system |
|
| central nervous system |
|
| The cardiovascular system |
|
| Musculoskeletal system |
|
| Are common |
|
Overdose
The instructions for use indicate that in case of an overdose of Trandolapril, the development of the following symptoms is observed:
- severe decrease in blood pressure;
- Quincke's edema.
Gastric lavage should be done as soon as possible. In cases of overdose, the patient's stomach must be rinsed. In this case, the dosage of the drug should be reduced or completely discontinued. If blood pressure has dropped significantly, doctors administer sodium chloride intravenously. In case of an overdose of Trandolapril, first place the patient in a horizontal position and raise his legs, then immediately call an ambulance.
ACE inhibitors are most widely used to treat heart failure and hypertension.
ACE inhibitors include the substance trandolapril.
This component, which has a hypotensive and vasodilating effect, is included in drugs for secondary prevention of heart failure after myocardial infarction, treatment of hypertension and heart failure.
Medicines based on trandolapril are prescribed to adult patients. Dispensed from pharmacies by prescription.
pharmachologic effect
It is an ACE inhibitor. It has a vasodilating and hypotensive effect. Helps suppress the formation of angiotensin II and reduce the release of aldosterone.
Dilates veins to a lesser extent than arteries. Reduces post- and preload, blood pressure, peripheral resistance. There is no reflex increase in heart rate. Increases the synthesis of propylene glycol, reduces the degradation of bradykinin.
There is no connection between the activity of plasma renin and the hypotensive effect: with normal or reduced concentrations of the hormone, blood pressure decreases, which is due to the effect on the tissue renin-angiotensin system. With prolonged use, the severity of myocardial hypertrophy and the walls of resistive arteries decreases.
Strengthens renal and coronary blood flow. Leads to improved blood supply to ischemic myocardium. Increases the concentration of phosphocreatine in reperfusion ischemic zones of the myocardium.
Delays potassium excretion, increases diuresis. Reduces platelet aggregation. In people who have had myocardial infarction, it slows down the development of LV dysfunction. In patients with CHF, it increases life expectancy.
A noticeable decrease in blood pressure is observed within two days.
Absorption from the gastrointestinal tract is rapid. Bioavailability does not change when consumed with food. Excreted in mother's milk. Excreted by the kidneys (33%) and through the intestines (67%).
Indications for use
Trandolapril is prescribed for the treatment of CHF (as a component of combination therapy), arterial hypertension, as well as for secondary prevention of HF after myocardial infarction.
Method of administration
Trandolapril capsules are taken regardless of meal time, with liquid. They swallow them whole. No matter how many mg of Trandolapril the doctor prescribes, the drug is taken once a day at the same time.
A specialist should select an individual dose of medication.
| Arterial hypertension | LV dysfunction after myocardial infarction |
In persons with arterial hypertension who are not taking diuretic medications, with normal liver and kidney function in the absence of CHF, the recommended starting dose ranges from 0.5 to 2 mg per day. The starting dose for black patients is usually 2 mg. The 0.5 mg dose was only effective in some people. The dose can be doubled after one to four weeks of therapy. The dose can be increased up to a maximum of 4-8 mg/day. If there is no effect or adequate response to the drug at a dose of 4-8 mg/day, combination treatment with calcium channel blockers and/or diuretics should be considered. | Treatment can begin on the third day after acute myocardial infarction. Begin therapy with 0.5-1 mg/day, after which the single daily dose is gradually increased to 4 mg. If therapy is poorly tolerated (the limiting point is the development of arterial hypotension), you can temporarily stop increasing the dose. With concomitant treatment with vasodilators, including diuretics and nitrates, the development of hypotension is a reason to reduce their dosage. As for the dosage of Trandolapril, it is reduced if it is impossible to change the concomitant treatment or the therapy is ineffective. |
Release form, composition
Available in capsules or tablets. The active ingredient is trandolapril.
Interaction with other drugs
The effect of Trandolapril is enhanced by alcoholic drinks, diuretics, and other antihypertensive drugs, including beta-blockers.
The effect of Trandolapril is weakened by NSAIDs, estrogens and drugs that activate the renin-angiotensin-aldosterone system.
Myelosuppressants increase the likelihood of developing agranulocytosis and/or fatal neutropenia; procainamide and allopurinol – neutropenia.
Potassium-sparing diuretics (triamterene, amiloride, spironolactone, etc.), potassium supplements and other potassium-containing products, salt substitutes and cyclosporine increase the likelihood of hyperkalemia.
Antacids enhance absorption.
Trandolapril potentiates the inhibitory effect of alcohol on the central nervous system, increases the toxic effect of lithium by increasing its concentration, and reduces diuretic-induced hypokalemia and the symptoms of hyperaldosteronism.
Side effects
| Blood (hemostasis, hematopoiesis), cardiovascular system | chest pain, a sharp decrease in blood pressure (especially during treatment with diuretics, impaired water-salt metabolism), tachy- and bradycardia, palpitations, angina pectoris, decreased hematocrit and hemoglobin levels, neutro- and/or leukopenia, arrhythmias, myocardial infarction, agranulocytosis, anemia (sometimes hemolytic), thrombocytopenia, eosinophilia. |
| Sense organs, nervous system | headaches, depression, dizziness, fainting, cerebral stroke, blurred vision, paresthesia, convulsions, balance and/or sleep disturbances, loss of taste. |
| Skin | psoriatic skin changes, bullous pemphigus, baldness, allergic skin reactions, photosensitivity, rash. |
| Gastrointestinal tract | dyspepsia, glossitis, vomiting, abdominal pain, impaired liver function (fulminant liver necrosis with fatal outcome, cholestatic jaundice), constipation or diarrhea, pancreatitis, hepatitis, dry mouth, intestinal obstruction. |
| Respiratory system | dry cough, bronchospasm, sinusitis, lower and upper respiratory tract infections, dyspnea, rhinitis, bronchitis. |
| Genitourinary system | decreased libido, impaired renal function (proteinuria, acute renal failure), impotence, edema. |
| Musculoskeletal system | arthralgia, convulsions, myalgia, arthritis. |
| Others | angioedema, hyponatremia, hyperproteinemia, development of infections, uratemia, hyperkalemia, increased concentrations of bilirubin, creatinine, liver enzymes in the blood serum. |
Overdose
Manifested by angioedema and acute arterial hypotension.
It is treated by completely withdrawing the drug or reducing its dose, gastric lavage, transferring the patient to a horizontal position, taking measures to increase blood volume (transfusion of other blood replacement fluids, administration of saline solution.
Symptomatic therapy involves the administration of hydrocortisone (IV), epinephrine (IV or SC), as well as the prescription of antihistamines.
Contraindications
Trandolapril is not prescribed to pregnant women, people with hypersensitivity to trandolapril or other ACE inhibitors, or nursing patients.
Caution is required when using the medicine when:
During pregnancy
Prescription to pregnant patients is unacceptable.
Breastfeeding is stopped during therapy.
Conditions and shelf life
Stored at temperatures up to 30 degrees for three years.
Price
The cost of a medicine is determined by its trade name. Approximate price of drugs containing trandolapril in Russia, is 500 rub. per package.
Medicines containing trandolapril in Ukraine sold at prices from 60 to 850 UAH. for one pack.
Analogs
Analogues of Trandolapril include Gopten, Trandolapril Ratiopharm, as well as the combination drug Tarka, which additionally contains verapamil.
Trandolapril is one of the inhibitors used to treat hypertension and heart failure. The drug has a high level of safety during therapy; it can be used both as an independent drug and in combined treatment of diseases. Before you start taking it, it is recommended to carefully read the instructions for use and dosage.
Description of the drug
Trandolapril is available in the form of red tablets and capsules. The medicine is sold in cardboard packages, inside of which there are blisters with tablets.
The active component of the drug is trandolapril, the content of which in one tablet is 2 mg.
The drug also contains corn starch, povidone, and glucose monohydrate. The capsule shell consists of gelatin and titanium dioxide. It is recommended to store the medication in a place protected from sunlight, at a temperature not exceeding 30 degrees Celsius. The chemical formula of the drug is shown below in the illustration.
Mechanism of action
Trandolapril has 
pronounced hypotensive effect, has a beneficial effect on the production of aldosterone, reducing it. For the most part, the capsules dilate the veins, but have a lesser effect on the arteries.
Taking the medication allows you to reduce fasting load. Trandolapril significantly reduces the level of bradykinin degradation. When plasma renin levels are normal, blood pressure begins to decrease. A long course of treatment with the drug can eliminate the symptoms of hypertrophy of the myocardium and arterial walls.
Taking the drug increases renal blood flow, which in turn improves blood supply and oxygen enrichment of the myocardium. Taking capsules may cause potassium retention in the body.
Trandolapril significantly reduces platelet aggregation. A noticeable effect of the capsules on the patient’s body is observed 2 days after the first dose. Trandolapril increases life expectancy and slows down the development of ventricular dysfunction.
The capsules are quickly absorbed and can be taken with or without food. This does not affect the effectiveness of the drug.
The medication is eliminated from the body through the kidneys and intestines. The active components can pass into mother's milk, which is why there are restrictions on taking the drug during breastfeeding.
Indications and method of use
Trandolapril is necessary 
take if the patient suffers from arterial hypertension or heart failure. Capsules are taken orally; they must be washed down with a sufficient volume of liquid, without chewing. You can take the medication without focusing on food intake.
The dosage of the drug may vary, but regardless of this, capsules can only be taken once a day. The medication should be taken at approximately the same time. The dosage of the medication is determined by the attending doctor, based on the type of patient’s illness and general condition.
Trandolapril instructions for use:
- For hypertension, the initial dosage of the drug varies from 0.5 mg to 2 mg per day. Provided that the patient does not have problems with the liver and kidneys, as well as diseases of the cardiovascular system. The dosage is indicated for patients who do not take capsules together. The starting dosage for African Americans is 2 mg. The minimum dose of 0.5 mg is not effective in this case. If the required therapeutic effect has not been achieved, then the dosage is increased to 4-8 mg per day. However, this must be done after 2-3 weeks of use.
If the patient’s condition does not improve, then combination therapy using other medications, including calcium channel blockers, is prescribed;
- After myocardial infarction and in case of ventricular dysfunction, capsules can be taken only a few days after the heart attack, the starting dosage is 0.5-1 mg per day. Then the dosage is gradually increased to 4 mg. If the patient does not tolerate an increase in the amount of mg of the drug per day, then the drug can be temporarily stopped or returned to the use of 1 mg per day;
- Taking Trandolapril in elderly patients - if patients do not have liver dysfunction, then adjustment of the dose used is not necessary. With particular caution, it is necessary to increase the dosage for those people who have heart defects, kidney failure, or while taking diuretics;
- When taking other diuretics - for patients who have severe water-salt imbalance, diuretics should be discontinued a few days before the start of the course of capsule treatment. This will reduce the risk of concomitant development of hypertension;
- For heart failure, the initial dosage of the drug will be 0.5 mg. The patient must be under the constant supervision of a doctor in the hospital. If the body reacts positively, the dosage may be increased;
- In case of renal failure - for patients with mild symptoms of the disease, the dosage is not subject to adjustment. If the clearance level of creatine reaches 30 ml/min, then the initial dose should not exceed 0.5 mg per day. Then it can gradually increase as prescribed by the doctor;
- In case of liver failure, treatment with Trandolapril is prescribed with extreme caution; a minimum dosage of 0.5 mg is used with the possibility of gradual increase. The therapy is carried out under the supervision of a doctor.
When is the drug prohibited?
Contraindications to the use of capsules are personal intolerance to the components of the medication, the presence of angioedema, and insufficient age (under 18 years).
The active components of the drug can pass through breast milk and the placental barrier, so taking Trandolapril can only be prescribed as a last resort, when the benefits of its use by a woman far outweigh the possible risks for the child.
In case of an overdose of the drug, tachycardia, shock, a sharp decrease in blood pressure, and electrolyte disturbances are observed. In this case, refusal to take capsules and symptomatic treatment is necessary.
Studies have shown that the use of the drug can lead to the following side effects:
Important Information
Taking capsules can cause dizziness and decreased concentration, so during treatment it is recommended to avoid driving and operating machinery that requires a quick response from a person. While taking Trandolapril, you must avoid alcoholic beverages, which can cause side effects.
It is also recommended to eat a healthy diet and follow the doctor’s instructions regarding your diet. During treatment, it is important to control your weight, keeping it at the desired level if it corresponds to the norm, and reducing it if it is excessive.
Can Trandolapril be taken with other medications?
Complex treatment with capsules and other drugs requires a well-chosen combination of medications, otherwise they can inhibit each other’s action and cause the development of side effects. Taking Trandolapril with other diuretics may cause an enhanced hypotensive effect.
Drugs containing potassium may be dangerous for those patients who have renal failure. Therefore, complex therapy should be carried out under the supervision of a doctor with the selection of a personal dosage.
The simultaneous use of capsules and drugs aimed at lowering blood sugar levels can lead to the development of hypoglycemia. Medicines containing lithium lead to lower excretion of lithium from the body.
Trandolapril - prices and analogues
for Russian patients varies between 550-600 rubles per package of medication. If taking capsules causes negative reactions from your body, then you can try replacing it with similar products that have a similar effect:
- Quinafar;
- Akurenal;
- Berlipril;
- Vitopril;
- Dapril;
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