Dropped
Active material: Trandolapril, Verapamil
When ATH: C09BB10
CCF: Antihypertensive drugs
ICD-10 codes (testimony): I10
When CSF: 01.09.16.04
Manufacturer: ABBOTT GmbH & Co. KG (Germany)
PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING
Capsules of the prolonged action hard gelatin, size 0, opaque, pale pink; contents of capsules – White granules (trandolapril) and white pills (verapamil hydrochloride) oblong shape with biconvex film coated.
| 1 caps. | |
| trandolapril | 2 mg |
| verapamil hydrochloride | 180 mg |
Excipients: granules – corn starch, lactose monohydrate, povidone (K30), sodium fumarate; tablets – microcrystalline cellulose, sodium alginate, povidone (K30), magnesium stearate, Purified water.
The composition of the film coating of tablets: gipromelloza 6 mPa, gipromelloza 15 mPa, giproloza 7 mPa, macrogol 400, macrogol 6000, talc, colloidal silicon dioxide, sodium docusate, Titanium dioxide (E171).
The composition of the shell capsules: Titanium dioxide (E171), iron oxide red dye, gelatin, sodium lauryl.
5 PC. – blisters (1) – cardboard boxes.
5 PC. – blisters (2) – cardboard boxes.
5 PC. – blisters (3) – cardboard boxes.
5 PC. – blisters (4) – cardboard boxes.
7 PC. – blisters (1) – cardboard boxes.
7 PC. – blisters (2) – cardboard boxes.
7 PC. – blisters (3) – cardboard boxes.
7 PC. – blisters (4) – cardboard boxes.
10 PC. – blisters (1) – cardboard boxes.
10 PC. – blisters (2) – cardboard boxes.
10 PC. – blisters (3) – cardboard boxes.
10 PC. – blisters (4) – cardboard boxes.
14 PC. – blisters (1) – cardboard boxes.
14 PC. – blisters (2) – cardboard boxes.
14 PC. – blisters (3) – cardboard boxes.
14 PC. – blisters (4) – cardboard boxes.
Pharmacological action
Combined antihypertensive drug, containing an ACE inhibitor and a calcium channel blocker slow prolonged action.
Trandolapril
It represents the ethyl ester (prodrug) nesulfgidrilnogo ACE inhibitor trandolaprilata. Podavlyaet activity has sistemы renin-angiotensin-alydosteronovoy sistemы plazmы Resurrection. Renin – enzyme, which is synthesized by the kidney and enters the bloodstream, which causes the conversion of angiotensinogen to angiotensin I (maloaktivnый decapeptide). The latter is converted under the action of ACE (peptidildipeptidazy) in angiotensin II – a powerful vasoconstrictor, causing narrowing of the arteries and increased blood pressure, and also stimulates aldosterone secretion by the adrenal glands.
Inhibition of ACE reduces the concentration of angiotensin II in plasma, which is accompanied by a decrease in vasopressor activity and aldosterone secretion. Although the production of aldosterone is reduced to a small extent, Nevertheless there may be a slight increase in serum potassium concentration in combination with the loss of sodium and water.
The reduction of angiotensin II on a feedback mechanism leads to increased activity of renin in blood plasma. Another function of the ACE is to destroy kininov (bradykinin), with strong vasodilating properties, to inactive metabolites. In this regard, ACE inhibition leads to increased levels of circulating and tissue kallikrein-kinin, which promotes vasodilation by the activation of prostaglandin. This mechanism, perhaps, partly defines the hypotensive effect of ACE inhibitors and is the cause of some adverse effects.
In patients with hypertension, ACE inhibitors leads to a comparable decrease in blood pressure in the sitting and standing without a compensatory increase in heart rate. PR decreases, cardiac output remains unchanged or increases. Renal blood flow increases, and glomerular filtration rate is usually unchanged. In some cases, the optimal control of blood pressure can achieve in just a few weeks after starting treatment. When long-term therapy hypotensive effect persists. Trandolapril does not impair the circadian blood pressure profile.
Abrupt discontinuation of treatment is not accompanied by a rapid increase in blood pressure. The antihypertensive effect of trandolapril is evident within 1 hours after administration and lasts for at least 24 no, wherein trandolapril no effect on circadian blood pressure profile.
Verapamil
Blocks transmembrane current of calcium ions into smooth muscle cells of the myocardium and coronary vessels. It causes a decrease in blood pressure at rest and during exercise due to the expansion of peripheral arterioles. As a result, reducing PR (afterload) decreases myocardial oxygen demand and energy consumption. It reduces myocardial contractility. The negative inotropic effect of the drug can be compensated by a decrease in systemic vascular resistance. Cardiac index is not reduced, except in patients with left ventricular dysfunction.
Verapamil does not affect the sympathetic regulation of cardiac activity, because not block the β-adrenergic receptors.
Dropped
In studies in healthy human volunteers showed no signs of interaction between verapamil and trandolapril at pharmacokinetic parameters or the renin-angiotensin system. Hence, synergies two drugs reflects their complementary pharmacodynamic effects. In clinical studies, the drug Tarka reduced BP to a greater extent, than either agent alone.
Pharmacokinetics
Trandolapril
Absorption
After oral trandolapril is rapidly absorbed from the gastrointestinal tract. The absolute bioavailability of approximately 10%. Tmax in the blood plasma of about 1 no.
Distribution
Binding trandolapril plasma proteins is approximately 80% and does not depend on the concentration of. Vd trandolapril about 18 l. T1/2 <1 no. Repeated use of Css It reached approximately 4 day, in healthy volunteers, and in patients younger and older with hypertension.
Metabolism
The plasma trandolapril is hydrolyzed to form the active metabolite trandolaprilata. Tmax trandolaprilata in plasma is 4-10 no. Cmax or AUC is independent of the meal. The absolute bioavailability of about trandolaprilata 70%. Binding to blood proteins depends on the concentration and varies from 65% at concentrations 1000 ng / ml to 94% at concentrations 0.1 ng / ml. Trandolaprilat it has high affinity for ACE.
Deduction
Renal clearance varies from trandolaprilata 1 to 4 l / h, depending on dose. При Css Effective T1/2 trandolaprilata together with a small fraction of the drug received varied between 16 and h 24 no, probably, reflecting binding to plasma and tissue ACE. In a trandolaprilata urine output 10-15% dose of trandolapril, <0.5% the dose is excreted in the urine as unchanged. Upon receiving the labeled trandolapril inside 33% radioactivity detected in urine and 66% – Calais.
Pharmacokinetics in special clinical situations
The pharmacokinetics of trandolapril has not been studied in children and adolescents under the age of 18 years.
Trandolapril concentration in blood plasma increases in elderly patients (senior 65 years). However, the plasma concentration trandolaprilata and ACE-inhibitory activity in patients with hypertension elderly of both sexes identical.
Compared with healthy volunteers, patients on hemodialysis and QC <30 ml / min, the plasma concentration of approximately trandolaprilata 2 times higher, and renal clearance decreased by approximately 85%.
Compared with healthy volunteers, patients with a mild alcoholic cirrhosis and trandolapril plasma concentration increases trandolaprilata 9 and 2 fold, respectively, but the ACE-inhibitory activity does not change.
Verapamil
Absorption
After oral administration about 90-92 % dose of verapamil is rapidly absorbed in the small intestine. Bioavailability is all 22% because of the pronounced effect “first pass” through the liver. Repeated use of the mean bioavailability can be increased to 30%. The time to reach Cmax Plasma is 4-15 no.
Distribution
Css with repeated application 1 time / day achieved through 3-4 day. Binding to plasma proteins is approximately 90%.
Metabolism
One of 12 metabolites, discovered in the urine, It is norverapamil, pharmacological activity which is 10-20% from that of verapamil; its share is 6% from the output of the drug. Css norverapamila and verapamil similar.
Deduction
T1/2 with repeated use is equal to the average 8 no. In unchanged form excreted in the urine 3-4% dose. The metabolites are excreted in the urine – 70%, faeces – 16%.
Pharmacokinetics in special clinical situations
The pharmacokinetics of verapamil does not change with impaired renal function. Renal function does not affect the removal of verapamil.
Bioavailability and T1/2 verapamil are increased in patients with liver cirrhosis. However, the pharmacokinetics of verapamil remained unchanged in patients with compensated liver dysfunction.
Dropped
Information on the pharmacokinetic interactions between verapamil and trandolapril / trandolaprilatom not available, therefore, the pharmacokinetics of both drugs with combined application does not differ from that in appointing them individually.
Testimony
- Essential hypertension (patients, which shows the combination therapy).
Dosage regimen
The drug is taken orally by 1 caps. 1 time / day, preferably in the morning after a meal. The capsule is swallowed whole, drinking water.
Side effect
The table below shows adverse reactions, that were possibly or probably related to the use of the drug Tarka and observed more than 1% patients. All reactions were divided in frequency >1/100, but <1/10.
| Organ system | Frequency | Side effects |
| From the central and peripheral nervous system | often | headache, dizziness |
| Cardio-vascular system | often | AV block I degrees |
| The respiratory system | often | increased cough |
| From the digestive system | often | constipation |
| Other | often | asthenia / slabosty |
Other clinically relevant side effects
The respiratory system: bronchitis, breathlessness, nasal sinuses.
From the hematopoietic system: leukopenia, neutropenia, lymphopenia, thrombocytopenia.
Metabolism: hyperkalemia, giponatriemiya.
From the central and peripheral nervous system: alarm, imbalance, insomnia, paresthesia, gipesteziya, drowsiness, fainting, aphronia.
From the senses: visual impairment, mist, dizziness (laʙirintnoe), noise in ears.
Cardio-vascular system: complete AV-block, bradycardia, palpitations, hypotension, tides, angina, tachycardia, bundle-branch block, acute myocardial infarction, ventricular premature beats, nonspecific ST-segment changes on ECG T.
From the digestive system: rarely – nausea, diarrhea, dyspepsia, dry mouth.
On the part of the musculoskeletal system: artralgii, mialgii, gout (hyperuricemia).
From the urinary system: increased urination, polyuria, hematuria, proteinuria, nocturia.
On the part of reproduktivoy: impotence, endometriosis.
From the laboratory parameters: LDH increase, Alkaline phosphatase, IS, ALT and / or bilirubin, serum creatinine, BUN.
Allergic reactions: angioedema, itch, rash.
Other: chest pain, peripheral edema, fatiguability.
Side effects, observed when using verapamil hydrochloride
Cardio-vascular system: AV-блокада I, II или III степени, blockade of the sinus node, may develop or increase in heart failure, AV диссоциация, intermittent claudication, angina, arrhythmia, pulmonary edema, tachycardia, bradycardia, severe hypotension, tides.
From the central and peripheral nervous system: acute ischemic stroke, confusion, drowsiness, psychotic symptoms, tremor, headache, dizziness, paresthesia.
From the digestive system: giperplaziya right, pain or abdominal discomfort, reversible obstructive ileus, nausea, vomiting, constipation; increase in liver enzymes.
On the part of the endocrine system: gynecomastia, galactorrhea, hyperprolactinemia, increased perspiration.
From the urinary system: frequent urination.
On the part of the musculoskeletal system: muscular weakness, myalgia, arthralgia.
From the senses: System dizziness.
Reproductive system: impotence.
Dermatological reactions: ecchymosis, bruising, hair loss, hyperkeratosis, purpura.
Allergic reactions: hypersensitivity reactions, hives, itching, erythema multiforme, maculo-papular rash, Stevens-Johnson syndrome, angioedema.
Other: peripheral edema, fainting, fatigue.
Side effects, observed when using trandolapril
From the digestive system: vomiting, stomach ache, pancreatitis.
Other: agranulocytosis, hypersensitivity reactions, alopecia, fever, decreased libido.
Side effects, observed when using all ACE inhibitors
CNS: transient ischemic attack, headache.
Cardio-vascular system: myocardial infarction, cardiac arrest, cerebral hemorrhage, hypotension.
From the hematopoietic system: pancytopenia, reduction of hemoglobin and hematocrit, neutropenia, agranulocytosis.
From the digestive system: diarrhea, nausea, ageusia, pancreatitis.
From the urinary system: acute renal failure.
Allergic reactions: erythema multiforme, toxic epidermal necrolysis, angioedema, rash.
Other: chest pain, cough, hyperkalemia.
Contraindications
- Cardiogenic shock;
- Acute myocardial infarction;
— AV-blockade II and III degrees (except in patients with a functioning pacemaker);
- SSS (except in patients with a functioning pacemaker);
- Atrial fibrillation / atrial flutter in patients with WPW syndrome and LGL;
- Acute heart failure;
- Chronic heart failure II B and stage III;
- Vыrazhennaya bradycardia;
- Severe hypotension;
- Renal dysfunction (CC<30 ml / min.);
- Simultaneous use of beta-blockers;
- Angioedema when using an ACE inhibitor (history);
- Pregnancy;
- Lactation (breast-feeding);
- Childhood and adolescence up 18 years;
- Hypersensitivity to trandolapril or any other ACE inhibitors.
Carefully use in patients with aortic stenosis, hypertrophic obstructive cardiomyopathy, hepatic dysfunction and / or kidney, systemic connective tissue diseases (incl. SLE, scleroderma), suppression of bone marrow hematopoiesis, AV-blockade I degree, ʙradikardii, hypotension, states, accompanied by a decrease in the bcc (incl. diarrhea, vomiting), bilateral renal artery stenosis, stenosis of the artery to a solitary kidney, condition after kidney transplantation, patients, a diet with restriction of salt, hemodialysis, the combined use of diuretics.
Pregnancy and lactation
Do not use this drug during pregnancy and lactation (breast-feeding).
The safety of the drug Tarka in pregnant women has not been established. There are some observations of neonatal lung hypoplasia, intrauterine growth retardation, ductus arteriosus and hypoplasia of the skull after ACE inhibitors during pregnancy. ACE inhibitors can cause hypotension, accompanied by anuria in the fetus or newborn, or oligogidroamnionom.
The risk of teratogenic effects is highest in the appointment of ACE inhibitors in the II and III trimester of pregnancy. Information about the possibility of teratogenicity or embryo / fetotoxicity ACE inhibitors in the I trimester of pregnancy is not available.
Verapamil is excreted in breast milk. If necessary, use Tarka during lactation should decide the issue of termination of breastfeeding.
Cautions
Patients with hepatic impairment need careful monitoring during treatment with Tarka.
In patients with uncomplicated hypertension After the first dose of trandolapril, as well as the increase observed after the development of arterial hypotension, accompanied by clinical symptoms. The risk of hypotension higher in violation of water-electrolyte balance as a result of prolonged diuretic therapy, limit salt intake, dialysis, diarrhea or vomiting. In such patients before treatment should be discontinued trandolapril therapy with diuretics and fill BCC and / or salt content. Blood pressure should be monitored carefully in the appointment or revocation of NSAIDs during the drug Tarka.
When ACE inhibitors are described cases of agranulocytosis and bone marrow suppression. These adverse events were more common in patients with impaired renal function, especially in systemic connective tissue diseases. In such patients (eg, SLE or scleroderma) advisable to regularly monitor the number of leukocytes in the blood and urine protein, especially with impaired renal function, treatment of GCS and cytostatics, antimetabolites.
Trandolapril may cause angioneurotic edema of the face, language, pharynx and / or larynx.
The preparation includes verapamil Tarka, Therefore, the use of combined drug should be avoided in patients with severe left ventricular dysfunction (eg, with ejection fraction <30%, increase in pulmonary capillary wedge pressure >20 mm Hg. Article. or severe symptoms of heart failure) and patients with any degree of left ventricular dysfunction, if they receive a beta-blocker.
In a study of patients with hypertension should always assess kidney function. In patients with chronic heart failure, bilateral renal artery stenosis or unilateral renal artery stenosis in a solitary kidney patients (eg, after transplantation) increased risk of renal dysfunction, and in patients with renal insufficiency – the risk of further deterioration of renal function.
Some patients with hypertension, without kidney disease, when assigning trandolapril in combination with a diuretic may be an increase in blood urea nitrogen and serum creatinine.
In patients with hypertension, particularly with impaired renal function, Tarka medication can cause hyperkalemia.
When surgical interventions or general anesthesia with the use of drugs, causing hypotension, trandolapril may block the formation of angiotensin II, associated with compensatory renin release.
Precautions should select doses of inhaled anesthetics, while the use of verapamil.
Not recommended simultaneous application of verapamil and colchicine because of the possibility of tetraparesis.
Some patients, receiving diuretics, especially recently, after the appointment of trandolapril, a sharp decrease in blood pressure.
Since the data on the interaction of verapamil and disopyramide are missing, disopyramide not be used for 48 hours prior to or 24 hours after administration of verapamil.
Use in Pediatrics
Do not use the drug has been studied in Tarka and pediatric patients up to age podrostkovovgo 18 years, therefore its use in this age group is not recommended.
Effects on ability to drive vehicles and management mechanisms
It should refrain from driving and using machinery from the early stages of treatment, because the ability to drive or use complex technology may deteriorate.
Overdose
In clinical studies, the maximum dose of trandolapril was 16 mg. At the same time there were no signs of his intolerance.
If overdose Tarka, the following symptoms, caused verapamila gidroxloridom: hypotension, AV блокада, bradycardia, asistolija. Cases of death.
If overdose Tarka, the following symptoms, caused trandolapril: severe hypotension, shock, stupor, bradycardia, electrolyte abnormalities, renal failure.
Treatment: removal of the drug, symptomatic therapy. Treatment of an overdose of verapamil hydrochloride includes parenteral administration of calcium supplements, use of beta-agonists, and gastric lavage. Given the slow exhaustion of the prolonged action of the drug should be monitored for the patient's condition 48 no: may require hospitalization. Verapamil hydrochloride is not removed by hemodialysis.
Drug Interactions
Interaction, caused by verapamil
Исследования in vitro indicates, that verapamil is metabolized by CYP3A4 isoenzymes action, CYP1A2, CYP2C8, CYP2C9 and CYP2C18.
Verapamil is an inhibitor of CYP3A4. Clinically significant interaction was observed while the use of inhibitors of CYP3A4, while there was an increase in plasma levels of verapamil blood, while inducers of CYP3A4 reduces the concentration of verapamil in plasma. Respectively, while the use of such funds should take into account the possibility of interaction.
The table summarizes data on the drug interaction, Conditionality verapamil
| Preparation | Possible effect on verapamil or verapamil to another drug while the application |
| Alpha-blockers | |
| Prazosin | Increase Cmax prazosin (40%), It does not affect the T1/2 prazosin. |
| Terazosin | Increased terazosin AUC (24%) and Cmax (25%). |
| Antiarrhythmics | |
| Flekainid | Minimal effect on the plasma clearance of flecainide (<10%); no effect on plasma clearance of verapamil. |
| Quinidine | Reduced oral quinidine clearance (35%). |
| Means for treatment of bronchial asthma | |
| Theophylline | Reducing oral and systemic clearance (20%). When smoking – decline 11%. |
| Anticonvulsants | |
| Carbamazepine | Increased AUC of carbamazepine (46%) in patients with refractory partial epilepsy. |
| Antidepressants | |
| Imipramine | Increased AUC of imipramine (15%), It does not affect the level of active metabolite, desipramine. |
| Hypoglycemic agents for oral | |
| Gliʙurid | Increased Cmax gliʙurida (28%), AUC (26%). |
| Antiinfectives | |
| Erythromycin | Perhaps the increase in verapamil. |
| Rifampicin | Reduced AUC (97%), Cmax (94%), bioavailability (92%) verapamil. |
| Telithromycin | Perhaps the increase in verapamil. |
| Antineoplastic agents | |
| Doxorubicin | Increases AUC (89%) and Cmax (61%) Doxorubicin when taking into verapamil in patients with small cell lung cancer. Introduction verapamil / in patients with progressive tumors did not affect the plasma clearance doxirubicin. |
| Barbiturates | |
| Phenobarbital | Increases oral verapamil clearance – in 5 time. |
| Benzodiazepines and other anxiolytics | |
| Buspirone | Increases in AUC and Cmax buspirone in 3.4 times. |
| Midazolam | Increases AUC (in 3 times) and Cmax (in 2 times) midazolama. |
| Beta-blockers | |
| Metoprolol | Increases AUC (32.5%) and Cmax (41%) metoprolol in patients with angina pectoris. |
| Propranolol | Increases AUC (65%) and Cmax (94%) propranolol in patients with angina pectoris |
| Cardiac glycosides | |
| Digitoxine | Decreases total clearance (27%) and extrarenal clearance (29%) digitoxin. |
| Digoxin | In healthy volunteers, increased Cmax (on 45-53%), Css (on 42%) и AUC ( on 52%) digoksina. |
| Histamine H2-receptors | |
| Cimetidine | Increases AUC R- and S-verapamil (25% and 40% respectively) a decrease in clearance of R- and S-verapamil. |
| Immunological agents | |
| Cyclosporine | Increases AUC, Css, Cmax (on 45%) cyclosporine. |
| Sirolimus | Perhaps the increase in sirolimus. |
| Tacrolimus | Perhaps the increase in tacrolimus. |
| Lipid-lowering agents, HMG-CoA reductase | |
| Atorvastatin | Perhaps the increase in atorvastatin. |
| Lovastatin | Perhaps the increase in lovastatin. |
| Simvastatin | Increases AUC (in 2.6 time) and Cmax (in 4.6 time) simvastatin. |
| Serotonin receptor antagonists | |
| Almotryptan | Increases AUC (20%) and Cmax (24%) almotrïptana. |
| Urikozuricheskih funds | |
| Sulfinpirazon | The increase in oral clearance of verapamil (in 3 times), reducing its bioavailability (60%). |
| Other | |
| Grapefruit juice | Increase in AUC R- and S-verapamil (49% and 37% respectively) and Cmax R- and S-verapamil (75% and 51% respectively). T1/2 and renal clearance were not changed. |
| St. John's wort | Reduced AUC R- and S-verapamil (78% and 80% respectively) with decreasing Cmax. |
While the use of the drug Tarka antiarrhythmic agents and beta-blockers may increase the adverse effects on the cardiovascular system (more pronounced AV-block, a significant decrease in heart rate, development of heart failure and increased arterial hypotension).
With simultaneous use of quinidine 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.
While the use of the drug prazosin Tarka, terazosin enhanced hypotensive effect.
While the use of the drug Tarka certain drugs for the treatment of HIV infection (ritonavir), can inhibit the metabolism of verapamil, which increases its concentration in blood plasma. With simultaneous use of verapamil dose should be reduced.
In an application with carbamazepine drug Tarka increased levels of carbamazepine in plasma, which may be accompanied by side effects typical of carbamazepine – diplopia, headache, ataxia, or dizziness.
In an application with lithium drug Tarka increased lithium neurotoxicity.
With simultaneous use of rifampicin with drug Tarka may decrease the hypotensive effect of verapamil.
In an application with sulfinpirazona drug Tarka may decrease the hypotensive effect of verapamil.
While the use of the drug Tarka effect of muscle relaxants may increase.
In an application with acetylsalicylic acid increases bleeding verapamil.
In an application with verapamil level of ethanol in the blood plasma increased.
The simultaneous use of verapamil may lead to increased serum levels of simvastatin or lovastatin.
Patients, receiving verapamil, treatment of HMG-CoA reductase (ie. simvastatin / lovastatin) It should start with the lowest possible dose with gradual increase in the course of their treatment. If you want to assign patients verapamil, already receiving HMG-CoA reductase, should be reviewed and accordingly reduce their concentration dose serum cholesterol. This tactic should be followed, while the appointment of verapamil with atorvastatin.
Fluvastatin, pravastatin and rosuvastatin are not metabolized by the action of isozymes CYP3A4, therefore their interaction with verapamil least likely.
Диуретики или другие гипотензивные лекарственные средства могут усилить гипотензивное действие трандолаприла. Трандолаприл может уменьшить потерю калия при совместном применении с тиазидными диуретиками.
Potassium-sparing diuretics (incl. spironolactone, amilorid, triamterene) или препараты калия повышают риск гиперкалиемии при одновременном применении с трандолаприлом.
Одновременное применение трандолаприла с гипогликемическими средствами (инсулином или пероральными гипогликемическими средствами) может усилить гипогликемический эффект и привести к повышению риска гипогликемии.
Трандолаприл может ухудшить выведения лития. Необходим контроль уровня лития в сыворотке крови.
При одновременном применении с верапамилом концентрация колхицина в крови может значительно повыситься, поскольку последний является субстратом для CYP3A и Р-гликопротеина, that, in turn, подавляют метаболизм верапамила.
В экспериментах на животных было показано, что ингаляционные анестетики снижают поступление кальция в клетку, оказывая угнетающее влияние на сердечно-сосудистую систему. При одновременном применении с верапамилом возможно усиление угнетающего действия на миокард.
Гипотензивный эффект некоторых ингаляционных анестетиков может быть усилен ингибиторами АПФ.
Следует избегать применения высокопроточных мембран из полиакрилонитрила во время гемодиализа у пациентов, receiving ACE inhibitors due to the possible development of anaphylactoid reactions.
NSAIDs reduce the antihypertensive effect of trandolapril.
Cytotoxic or other immunosuppressive drugs and corticosteroids increase the risk of leucopenia when used together with ACE inhibitors.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
The drug should be stored out of reach of children at or above 25 ° C. Shelf life – 3 year.
