Hapten
Producer: Abbott Laboratories (Abbott Leboratoriz) Netherlands
Code of automatic telephone exchange: C09AA10
Release form: Firm dosage forms. Capsules.
General characteristics. Structure:
Active agent: trandolaprit 0,5 mg.
Excipients: starch corn — 37,15 mg, lactoses monohydrate —
56,00 mg, povidone (K25) — 5,35 mg, the sodium stearylfumarating — 1,00 mg.
Solid gelatin capsule
Lid: gelatin — 15,6326 mg, titanium dioxide — 0,3194 mg, dye ferrous oxide yellow — 0,0160 mg, sodium lauryl sulfate — 0,0320 mg.
Case: gelatin — 23,6600 mg, titanium dioxide — 0,1600 mg, dye ferrous oxide yellow — 0,1320 mg, sodium lauryl sulfate — 0,0480 mg.
Description
Solid gelatin capsules No. 4 with the yellow opaque case and an opaque lid of color of ivory. Capsule contents — granules of white or almost white color.
Pharmacological properties:
Trandolapril is an ethyl ether (pro-medicine) of not sulphhydryl inhibitor of an angiotensin-converting enzyme (APF). Trandolapril is quickly soaked up and nonspecific hydrolyzed in традолаприлат (pharmacological an active metabolite).
Pharmacodynamics. Trandolaprilat densely contacts APF. The inhibition of APF leads to decrease in concentration of angiotensin II, Aldosteronum, atrial natriuretichesky factor and to increase in plasma activity of a renin and concentration of angiotensin I. Thus, trandolaprit modulates the renin-angiotensin-aldosteronovuyu system (RAAS) which plays the main role in regulation of the volume of the circulating blood (VCB), the arterial pressure (AP), and consistently has anti-hypertensive effect.
At patients with arterial hypertension use of a trandolapril in therapeutic doses leads to comparable decrease in the ABP in situation "lying" and "standing". The anti-hypertensive effect of a trandolapril is shown in 1 h after reception and remains within, at least, 24 hours. The maximum effect is reached in 8-12 h.
The data showing reduction of a hypertrophy of a myocardium together with improvement of diastolic function and increase in elasticity of arteries at people under the influence of a trandolapril are obtained.
Pharmacokinetics. Trandolapril is quickly soaked up after intake. Absolute bioavailability about 10%. Time of achievement of the maximum concentration (Cmax) was trandolaprit in a blood plasma by about 1 p.
Trandolapril is hydrolyzed to an active diatsidny metabolite of a trandolaprilat. Time of achievement of Cmax of a trandolaprilat in a blood plasma makes 3-8 h.
Communication trandolaprit about 80% with proteins of a blood plasma and does not depend on concentration. The volume of distribution (Vd) trandolaprit about 18 l. Elimination half-life (T1/2) less than 1 h. At repeated use the equilibrium condition of concentration is reached approximately in 4 days, both at healthy volunteers, and at patients of young and advanced age with arterial hypertension.
Cmax and AUC (the area under a curve "concentration time") do not depend on meal. Absolute bioavailability of a trandolaprilat at reception of a trandolapril makes about 13%. Communication with blood proteins depends on concentration and varies from 65% at concentration 1000 ng/ml to 94% at concentration of 0,1 ng/ml. At an equilibrium condition of concentration effective T1/2 of a trandolaprilat together with a small part of the accepted drug varies between 15 h and 23 h that probably reflects linkng with plasma and fabric APF. 10-15% of a dose of a trandolapril are removed in the form of a trandolaprilat by kidneys. After reception of a marked trandolapril in 33% it was removed through kidneys and 66% through intestines, in insignificant quantity it is removed in not changed look through kidneys (less than 0,5%).
The renal clearance of a trandolaprilat varies from 0,15 to 4 l/h depending on a dose.
The pharmacokinetics of a trandolapril was not studied at children more young than 18 years.
Concentration of a trandolapril in a blood plasma increases at elderly patients (65 years are more senior). However, plasma concentration of a trandolaprilat and it APF-ingibiruyushchaya activity at patients is comparable to arterial hypertension of advanced and young age.
Distinctions in pharmacokinetics of a trandolapril and trandolaprilat and APF — the inhibiting activity at patients with arterial hypertension of both floors were not observed.
Renal failure. In comparison with healthy volunteers, at the patients who are on a hemodialysis and with the clearance of creatinine (CC) less than 30 ml/min., plasma concentration trandolaprit and the trandolaprilata is approximately twice higher, and the renal clearance is reduced approximately by 85%.
Liver failure. In comparison with healthy volunteers, at patients with alcoholic cirrhosis in the initial or developed stage plasma concentration trandolaprit and the trandolaprilata raises in 9 and 2 times respectively, but APF-ingibiruyushchaya activity does not change.
Indications to use:
Essential hypertensia.
Dysfunction of a left ventricle after a myocardial infarction
The drug Gopten® improves postinfarction survival of patients with dysfunction of a left ventricle (fraction of emission of a left ventricle of £35%), irrespective of existence of symptoms of heart failure and/or ischemia.
At prolonged treatment by the drug Gopten® the general cardiovascular mortality, risk of sudden death and frequency of development of heart failure, heavy or resistant to treatment, considerably decreases.
Route of administration and doses:
Inside. The capsule is swallowed entirely and washed down with water. The drug Gopten® is accepted irrespective of meal, at the same time, once a day.
The doctor has to carry out selection of an individual dose of drug.
Arterial hypertension
At patients with arterial hypertension with normal function of kidneys and a liver, without symptoms of heart failure which are not accepting diuretic drugs, the recommended initial dose makes from 0,5-1 mg to 2 mg of 1 times a day. For patients of negroid race the usual initial dose makes 2 mg. Depending on clinical performance doubling of a dose is possible in 1-4 weeks of administration of drug of Gopten® to the maximum dose — 4-8 mg/days.
The maintenance dose makes 1-4 mg of 1 times a day. In the absence of therapeutic effect at use of the drug Gopten® in doses of 4-8 mg/days, it is necessary to consider the possibility of the combined tepariya with diuretics and/or blockers of "slow" calcium channels (BMKK).
Dysfunction of a left ventricle after a myocardial infarction
Treatment by drug Gopten can be begun with the day before yesterday after a myocardial infarction. The initial dose makes 0,5-1 mg a day, then the single day dose is gradually increased as much as possible to 4 mg. Depending on portability of therapy (the limiting moment — development of arterial hypotension) increase in a dose can be stopped temporarily. When developing arterial hypotension the accompanying therapy by vazodilatator, including nitrates and diuretics, should be reconsidered and, whenever possible, to lower their dosage. The dosage of the drug Gopten® should be reduced only if the previous measures were inefficient or impossible. Elderly patients
At patients of advanced age the same dosages of the drug ГоптенÒ, as at patients of young age are applied. With normal function of kidneys and the liver of dose adjustment is not required from elderly patients. With care and under control of the ABP it is necessary to increase a drug Gopten® dose at patients of advanced age with chronic heart failure, an abnormal liver function and/or kidneys or at the patients accepting diuretics.
The previous use of diuretics
Patients with risk of activation have system renin-angiotensin-aldosteronovoy (i.e. at patients with disturbance of a water salt metabolism) in 2 or 3 days before purpose of the drug ГоптенÒ in a dose of 0,5 mg it is necessary to cancel reception of diuretic drugs to reduce a possibility of development of arterial hypotension. Later, if necessary, it is possible to resume therapy by diuretics.
Heart failure
At patients with arterial hypertension and chronic heart failure without or with a renal failure, after an initiation of treatment APF inhibitors noted symptoms of arterial hypotension. At this group of patients therapy Gopten it is necessary to begin with drug with a dose 0,5 mg — 1 mg/days under careful observation of the doctor.
Renal failure
At patients with moderate insufficiency of function of kidneys (clearance of creatinine from 30 to 70 ml/min.) administration of drug in a usual dose is recommended. At clearance of creatinine less than 30 ml/min., an initial dose should not exceed 0,5 mg of 1 times a day. Further, if necessary the dose can be increased. Therapy by the drug ГоптенÒ at these patients has to be carried out under careful observation of the doctor.
Dialysis
The possibility of removal of a trandolapril or trandolaprilat at dialysis at patients is definitely not established. However it is possible to expect that concentration of an active metabolite — a trandolaprilat during dialysis decreases that can lead to increase in the ABP. Therefore at patients during dialysis careful monitoring of the ABP with possible correction in need of a drug dose is recommended.
Insufficiency of function of a liver
Patients with heavy insufficiency have functions of a liver, owing to decrease in hepatic clearance of a trandolapril and its active metabolite of a trandolaprilat, substantial increase in plasma of concentration both a trandolapril, and trandolaprilat can be observed (to a lesser extent). Treatment begin with a dose 0,5 mg a day under careful observation of the doctor.
Children
Drug use Gopten at children was not studied therefore its use for children is contraindicated.
Features of use:
General measures of precaution
At some patients receiving diuretics after purpose of the drug Gopten® excess decrease in the ABP can be observed.
Abnormal liver function
Trandolapril is pro-medicine which turns into an active form in a liver therefore it is necessary to observe extra care at patients with disturbance of its function. Such patients have to be under careful observation.
Arterial hypotension
At patients with uncomplicated arterial hypertension after reception of the first dose of the drug Gopten®, and also after its increase noted development of the arterial hypotension which was followed by clinical symptoms. Risk of arterial hypotension higher at patients with the hypovolemia and a hyponatremia which developed as a result of long diuretic therapy, restriction of consumption of table salt, dialysis, diarrhea or vomiting. At such patients before therapy with the drug Gopten® it is necessary to stop therapy by diuretics and to fill the volume of the circulating blood and/or content of salt.
Agranulocytosis/suppression of function of marrow
At treatment APF inhibitors described cases of an agranulocytosis and suppression of function of marrow. These undesirable phenomena meet at the patients with a renal failure who especially have diffusion diseases of connecting fabric more often. At such patients (for example, suffering from a system lupus erythematosus or a system scleroderma) reasonablly regularly to control number of leukocytes in blood and urine protein content, especially at a renal failure and treatment by glucocorticosteroids and antimetabolites.
Quincke's disease
The drug Gopten® can cause a Quincke's disease of the person, extremities, language, a throat and/or throat. The Quincke's disease at reception of APF inhibitors most often occurs at patients of negroid race.
At the patients accepting APF inhibitors the intestinal Quincke's disease was observed. It can be suspected at the patients accepting the drug Gopten® with an abdominal pain (both with nausea and vomiting, and without).
Renal failure
Less than 30 ml/min. can be required by patients with clearance of creatinine a drug Gopten® dose decline; function of kidneys should be monitorirovat carefully.
At patients with a renal failure, chronic heart failure, a bilateral or unilateral stenosis of renal arteries, at patients with one functioning kidney or after its transplantation the risk of deterioration in function of kidneys is increased. At some patients with arterial hypertension who do not have a disease of kidneys at purpose of the drug Gopten® in a combination with diuretic increase in an urea nitrogen of blood and serumal level of creatinine and a proteinuria can be observed.
Hyperpotassemia
At patients with arterial hypertension, especially with renal failures, the drug Gopten® can cause a hyperpotassemia.
Cough
At use of APF inhibitors there can be dry unproductive cough disappearing after therapy cancellation.
Surgical interventions / general anesthesia
At operative measures or the general anesthesia with use of the means causing arterial hypotension, the drug Gopten® can block the secondary formation of angiotensin II connected with compensatory emission of a renin.
Desensitization
When performing desensitization of an organism to poisons of animals at the patients receiving APF inhibitors development of anaphylactic reactions is possible (in certain cases — zhizneugrozhayushchy).
LPNP-aferez
When carrying out LPNP-aferez's at the patients receiving APF inhibitors development of zhizneugrozhayushchy anaphylactic reactions was observed.
Influence on ability to manage transport and to work with mechanisms
Proceeding from pharmacological properties of a trandolapril, the drug Gopten® should not influence ability to manage transport and to work with mechanisms. However at some patients, especially at the initial stages of treatment by APF inhibitors, or when replacing one drug by another, or at the patients taking alcohol rendering influence on ability to manage transport and to work with mechanisms is possible. Therefore after reception of the first dose of the drug ГоптенÒ or after increase in its dose, it is not recommended to manage within several hours motor transport or to work with mechanisms.
Side effects:
Side effects which were observed in clinical trials of a trandolapril at patients with arterial hypertension are presented in the table (easy and moderate severity). All reactions are distributed on systems of bodies and frequency of development (it is frequent ≥1/100, <1/10; infrequently ≥1/1000, <1/100).
System of bodies Frequency Undesirable effects
From a nervous system Often Headache, dizziness
From cardiovascular system Infrequently Heart consciousness
The expressed decrease in the ABP
From respiratory system Often Cough
From system of digestion Infrequently Nausea
From skin and hypodermic fabrics Infrequently Skin itch
Other Often Adynamy
Infrequently Weakness
In clinical trials at the patients with reduction of fraction of emission of a left ventricle after a myocardial infarction accepting trandolaprit, were often observed: dizziness, the expressed decrease in the ABP and cough.
The side effects observed in clinical trials at the patients with arterial hypertension or after a myocardial infarction accepting are given below trandolaprit. All reactions are distributed on systems of bodies and frequency of development (it is frequent ≥1/100, <1/10; infrequently ≥1/1000, <1/100, it is rare ≥1/10000, <1/1000).
System of bodies Frequency Undesirable effects
Infections and invasions Infrequently Upper respiratory tract infections
Seldom Upper respiratory tract infections
Bronchitis
Pharyngitis
From blood and lymphatic system Seldom Leukopenia
Deviations of standards of the contents
leukocytes and thrombocytes
From immune system Seldom hypersensitivity Reactions
From a metabolism and food Seldom Hyperglycemia
Giperurekimiya
Increase in appetite
Enzymatic dysfunction
From a nervous system Infrequently Sleeplessness
Seldom Drowsiness
Decrease in a libido
Uneasiness
Apathy
Disturbance of cerebral circulation
Syncope
Muscular spasms
Paresthesia
Migraine (with aura and without)
Taste disturbance
From sense bodys Infrequently Dizziness
Seldom Blepharitis
Hypostasis of a mucous membrane of an eye
Vision disorders
Diseases of eyes
Sonitus
From cardiovascular system Infrequently heat "Inflows"
Seldom Myocardial infarction
Myocardium ischemia
Ventricular tachycardia
Angiopatiya
Orthostatic hypotension
Peripheral vascular disorders
Varicosity
From a respiratory organs Infrequently Inflammation of upper respiratory tracts
Seldom Congestion of upper respiratory tracts
Pain in a stomatopharynx
Wet cough
Breath disturbances
From system of digestion Infrequently Diarrhea
Seldom Lock
Gastrointestinal disturbances
Abdominal pain
Hyperbilirubinemia
From skin and hypodermic fabrics Infrequently Skin rash
Seldom Quincke's disease
Hyperhidrosis
Skin diseases
From skeletal and muscular
system and connecting fabric Infrequently Dorsodynia and extremities
Seldom Spasms of muscles
Ostealgia
Osteoarthritis
From urinogenital system Infrequently Erectile dysfunction
Pollakiuria
Inborn, hereditary and
genetic disorders Seldom Inborn malformation of arteries
Ichthyosis
Other Infrequently Bol in a thorax
Seldom Peripheral hypostasis
Disturbance of health
Hypostasis
Fatigue
Injuries (including bruises, fractures)
Further the side effects registered at post-registration use of a trandolapril on systems of bodies are presented.
System of bodies Undesirable effects
From blood and lymphatic system Agranulocytosis, pancytopenia, hyperpotassemia.
From a nervous system of Tranzitornaya ischemic attack,
hematencephalon, balance disturbances.
From cardiovascular system Atrioventricular block,
cardiac standstill, arrhythmia.
From system of breath Bronchospasm.
From system of digestion Intestinal impassability, pancreatitis, jaundice.
From skeletal and muscular system of Mialgiya.
and connecting fabric
From skin and hypodermic fabrics Alopecia, small tortoiseshell, Stephens-Johnson's syndrome,
toxic epidermal necrolysis.
Other Fever.
Laboratory indicators
Increase in concentration in blood of creatinine, alkaline phosphotazy, an urea nitrogen, a lactate dehydrogenase (LDG).
Aberrations of indicators of an ECG, laboratory and functional trials of a liver.
Decrease in number of thrombocytes, hemoglobin, hematocrit. Increase in activity of transaminases: ALT (alaninaminotranspherase) and nuclear heating plant (aspartate aminotransferase).
The side effects relating to all APF inhibitors are listed below:
System of bodies Side effects
From blood and lymphatic system Hemolitic anemia.
From a nervous system Confusion of consciousness.
From sense bodys of Zatumanennost of sight.
From system of breath Sinusitis, rhinitis, glossitis.
From system of digestion Intestinal Quincke's disease.
From skin and hypodermic fabrics Erythema multiformny, psoriazopodobny dermatitis.
Interaction with other medicines:
Diuretics and other antihypertensives
Diuretics and other antihypertensives can strengthen anti-hypertensive action of a trandolapril. Beta adrenoblockers should be applied in a combination with trandolaprily only under careful observation of the doctor. Kaliysberegayushchy diuretics (Spironolactonum, amiloride, Triamterenum) or drugs of potassium increase risk of a hyperpotassemia, especially at patients with a renal failure. Trandolapril can reduce loss of potassium at use of thiazide diuretics.
Hypoglycemic means
Simultaneous use of a trandolapril, as well as any APF inhibitors, with hypoglycemic means (insulin or hypoglycemic means for intake) can strengthen hypoglycemic effect and lead to increase in risk of a hypoglycemia.
Lithium
Trandolapril can worsen lithium removal.
Others
When using during a hemodialysis of high-flowing membranes from polyacrylonitrile at the patients receiving APF inhibitors anaphylactoid reactions were described. Use of similar membranes should be avoided at purpose of APF inhibitors the patient who is on dialysis.
Non-steroidal anti-inflammatory drugs (NPVP) can reduce action of a trandolapril, however as well as other antihypertensives. Therefore at appointment or cancellation of NPVP at the patients accepting trandolaprit, careful control of the ABP is necessary.
APF inhibitors can strengthen anti-hypertensive action of some means for an inhalation anesthesia.
Allopyrinolum, cytostatics, immunodepressive means and system glucocorticosteroids or procaineamide can increase risk of development of a leukopenia at treatment by APF inhibitors.
Antacids can lower bioavailability of APF inhibitors.
The anti-hypertensive effect of APF inhibitors can be reduced at joint reception with sympathomimetics. Careful observation of patients is necessary.
Joint reception with neuroleptics and tricyclic antidepressants, also as well as with other antihypertensives increases risk of orthostatic hypotension.
At joint reception of APF inhibitors and injection drugs of gold (ауротиомалат sodium) nitritoidny reactions were in rare instances noted (rushes of blood to the person, nausea, vomiting and decrease in the ABP).
Clinically significant signs of interaction of a trandolapril from trombolitika, acetylsalicylic acid, beta adrenoblockers, blockers of "slow" calcium channels, nitrates, anticoagulants or digoxin at the patients with a left ventricular failure who had a myocardial infarction were not noted.
Clinically significant signs of interaction of a trandolapril with Cimetidinum were not revealed.
Contraindications:
Hypersensitivity to active agent or to any of excipients, hypersensitivity to other APF inhibitors, the Quincke's disease including connected with the previous treatment by APF inhibitors, a hereditary/idiopathic Quincke's disease, an aortal stenosis or obstruction of the taking-out path of a left ventricle, pregnancy, the breastfeeding period, age up to 18 years (efficiency and safety are not established), and also deficit of lactase, a lactose intolerance, a syndrome of glyukozo-galaktozny malabsorption.
With care
Abnormal liver function and/or kidneys (at clearance of creatinine less than 30 ml/min.), general diseases of connecting fabric (including a system lupus erythematosus, a scleroderma), a hyperpotassemia, oppression of a marrowy hemopoiesis, arterial hypotension, states which are followed by decrease in volume of the circulating blood (including diarrhea, vomiting, a diet with restriction of table salt and water, a hemodialysis), one or bilateral stenosis of renal arteries, a stenosis of an artery of the only kidney, a state after transplantation of a kidney, operative measures or the general anesthesia with use of the means causing arterial hypotension (prolonged treatment by diuretics), dry unproductive cough, simultaneous performing desensitization of an organism to poisons of animals, simultaneous carrying out LPNP-aferez (See the section "Special Instructions").
Use at pregnancy and during breastfeeding
Pregnancy
The drug Gopten® is contraindicated at pregnancy.
It is necessary to exclude existence of pregnancy before an initiation of treatment drug and to avoid approach of pregnancy during treatment.
Data on teratogenic effects of APF inhibitors in the I trimester of pregnancy are absent, however completely it is impossible to exclude such opportunity. At the patients planning pregnancy it is necessary to appoint hypotensive drugs for which safety of use during pregnancy was proved unless use of APF inhibitors is necessary. If pregnancy occurs in the course of APF inhibitor reception, it is necessary to cancel and appoint it immediately alternative therapy.
It is known that at use of APF inhibitors in II and the III trimester of pregnancy perhaps fetotoksichesky action (a renal failure, an oligoamnios, delay of ossification of bones of a skull) and toxic action (a renal failure, arterial hypotension, a hyperpotassemia) on the newborn child. In case of use of the drug Gopten® since the II trimester of pregnancy, ultrasonic assessment of function of kidneys of a fruit and a condition of a skull is recommended. Newborns whose mothers during pregnancy accepted APF inhibitors have to be under observation of the doctor for an exception of arterial hypotension.
Breastfeeding period
There are no data on penetration of a trandolapril into breast milk. The drug Gopten® is contraindicated during breastfeeding. More preferable to this group of patients to appoint drugs with the proved safety profile, especially when feeding newborn and premature children.
Overdose:
Overdose symptoms: the expressed lowering of arterial pressure, shock, a stupor, bradycardia, electrolytic disturbances, a renal failure.
Treatment: a symptomatic and maintenance therapy, including a gastric lavage and intestines, reception of absorbent carbon.
Storage conditions:
At a temperature not above 25 °C. To store in the place, unavailable to children. Term godnosti2 years. Not to apply after a period of validity.
Issue conditions:
According to the recipe
Packaging:
Capsules of 0,5 mg.
On 14 capsules in the blister from PVH/PVDH/Al — a foil. On 2 blisters together with the application instruction in a cardboard pack.
