Korvadil

General characteristics. Structure:

Active ingredient: 2,5 mg, 5 mg or 10 mg of an amlodipin (in the form of a bezilat).

Excipients: calcium hydrophosphate, magnesium stearate, cellulose microcrystallic, starch sodium glycollate, ferrous oxide red.

Anti-hypertensive drug.

Pharmacological properties:

Pharmacodynamics. Derivative dihydropyridine - the blocker of "slow" calcium channels (BMKK) of the II generation, has anti-anginal and hypotensive effect. Blocks calcium channels, reduces transmembrane transition of calcium ions to a cell (more in smooth muscle cells of vessels, than in cardiomyocytes).

Anti-anginal action is caused by expansion of coronary and peripheral arteries and arterioles: at stenocardia reduces expressiveness of ischemia of a myocardium; expanding peripheral arterioles, reduces the general peripheric vascular resistance (GPVR), reduces an afterload by heart, reduces the need of a myocardium for oxygen. Expanding coronary arteries and arterioles in not changed and in ischemic zones of a myocardium, increases intake of oxygen in a myocardium (especially at vasospastic stenocardia); prevents a spasm of coronary arteries (including caused by smoking). At patients with stable stenocardia the single daily dose increases tolerance to an exercise stress, increases time before an attack of stenocardia and an "ischemic" depression of a segment of ST, reduces the frequency of attacks of stenocardia and consumption of nitroglycerine and other nitrates.

Renders long-term dozozavisimy hypotensive effect. Hypotensive action is caused by direct vazodilatiruyushchy impact on unstriated muscles of vessels. At arterial hypertension the single dose provides clinically significant decrease in the ABP for 24 h (in position of the patient "lying" and "standing"). Orthostatic hypotension at purpose of an amlodipin meets rather seldom. Reduces degree of a hypertrophy of a myocardium of a left ventricle. Does not exert impact on contractility and conductivity of a myocardium, does not cause reflex increase in the heart rate (HR), slows down aggregation of thrombocytes, increases a glomerular filtration rate, possesses a weak natriuretic effect. At a diabetic nephropathy does not increase expressiveness of a microalbuminuria. Does not exert any adverse impact on a metabolism and concentration of lipids of a blood plasma and it can be applied at therapy of patients with bronchial asthma, a diabetes mellitus and gout. Significant decrease in the ABP is observed in 6-10 h, effect duration - 24 h.

At the patients with diseases of cardiovascular system (CCC) (including coronary atherosclerosis with defeat of one vessel and to a stenosis of the 3rd and more arteries, atherosclerosis of carotid arteries) who had a myocardial infarction, chrezkozhny transluminal angioplasty (TLAP) of coronary arteries or patients with stenocardia, use of an amlodipin prevents development of a thickening erotic-medii of carotid arteries, reduces a lethality from a myocardial infarction, a stroke, TLAP, aortocoronary shunting; leads to decrease in frequency of hospitalization concerning unstable stenocardia and progressing of chronic heart failure; reduces the frequency of the interventions directed to recovery of a coronary blood-groove.

Does not increase risk of death or development of complications and lethal outcomes at patients from chronic heart failure (the III-IV functional class on NYHA classification) against the background of therapy by digoxin, diuretics and inhibitors of an angiotensin-converting enzyme (APF). Patients from chronic heart failure (the III-IV functional class on NYHA classification) not ischemic etiology at use of an amlodipin have a probability of emergence of a fluid lungs.

Pharmacokinetics. After intake амлодипин it is slowly absorbed from the digestive tract (DT). Average absolute bioavailability makes 64%, Cmax in blood serum is observed in 6-9 h. Equilibrium concentration (Css) are reached after 7-8 days of therapy.

Meal does not influence absorption of an amlodipin. Average Vd makes 21 l/kg of body weight that indicates that the most part of drug is in fabrics, and smaller - in blood. The most part of the drug which is in blood (95%) contacts proteins of a blood plasma. Amlodipin is exposed to slow, but active metabolism in a liver in the absence of significant effect of "the first passing". Metabolites have no essential pharmacological activity.

After a single dose of T1/2 varies from 31 to 48 h, at repeated reception of T1/2 makes about 45 h. About 60% of the dose accepted inside are removed by kidneys preferential in the form of metabolites, 10% - in not changed look, and 20-25% - through intestines with bile. The general clearance of an amlodipin makes 0.116 ml / with/kg (7 ml/min., 0.42 l/h/kg).

At elderly patients (65 years are more senior) removal of an amlodipin is slowed down (T1/2 is 65 h) in comparison with young patients, however this difference has no clinical value. Lengthening of T1/2 at patients with a liver failure assumes that at prolonged use cumulation of drug in an organism will be higher (T1/2 - to 60 h). The renal failure has no significant effect on kinetics of an amlodipin.

Amlodipin gets through a blood-brain barrier. At a hemodialysis is not removed.

Indications to use:

Arterial hypertension (in monotherapy or in a combination with other anti-hypertensive means).

Stable angina of exertion and vasospastic stenocardia (in monotherapy or in a combination with other anti-anginal means).

Route of administration and doses:

Inside, once a day, washing down with a necessary amount of water (100 ml).

At arterial hypertension and stenocardia the initial dose makes 5 mg of 1 times in days. If necessary the daily dose can be increased to 10 mg, in one step.

At elderly patients. Корвадил® it is recommended to apply in an average therapeutic dose, dose adjustment is not required.

At patients with an abnormal liver function. In spite of the fact that T1/2 Korvadila®, as well as all BMKK, increases at patients with an abnormal liver function, dose adjustment usually is not required.

At patients with a renal failure. It is recommended to apply Korvadil® in usual doses, however it is necessary to consider possible insignificant increase in T1/2. Dose adjustment at co-administration with thiazide diuretics, beta adrenoblockers and APF inhibitors is not required.

Features of use:

Use at pregnancy and feeding by a breast. Safety of use of Korvadila® at pregnancy is not established therefore use at pregnancy is possible only in that case when the advantage for mother exceeds potential risk for a fruit.

Are absent this, testimonial of excretion of an amlodipin with breast milk. However it is known that other BMKK - dihydropyridine derivatives, are excreted with breast milk. In this connection, in need of purpose of Korvadila® in the period of a lactation it is necessary to resolve an issue of the breastfeeding termination.

Use at abnormal liver functions. With care to apply at abnormal liver functions.

Use at renal failures. At patients with a renal failure it is recommended to apply Korvadil® in usual doses, however it is necessary to consider possible insignificant increase in T1/2.

Use for children. It is contraindicated aged up to 18 years (efficiency and safety are not established).

Use for elderly patients. With care to apply at advanced age.

During therapy of Korvadilom® it is necessary to control the body weight and consumption of sodium, purpose of the corresponding diet is shown.

Maintenance of hygiene of an oral cavity and observation at the stomatologist is necessary (for prevention of morbidity, bleeding and a hyperplasia of gums).

At patients of advanced age T1/2 can increase and decrease clearance of drug. Change of doses is not required, but more careful observation of patients of this category is necessary.

With a low index of body weight and the patient with the expressed abnormal liver function the smaller dose of drug can be required by patients.

Efficiency and safety of use of Korvadila® at hypertensive crisis is not established.

Despite the absence of at BMKK of a syndrome of "cancellation", it is desirable to carry out the termination of treatment by Korvadil, gradually reducing a drug dose.

Influence on ability to control of motor transport and other difficult mechanisms: though against the background of reception of Korvadila® of any negative influence on ability to manage motor transport or other difficult mechanisms it was not observed, however, owing to possible excessive decrease in the ABP, development of dizziness, drowsiness and other side reactions, it is necessary to be careful in the listed situations, especially in an initiation of treatment and at increase in a dose.

Side effects:

Frequency of the side reactions given below was defined according to the following (classification of World Health Organization): very often - more than 1/10; often - from more than 1/100 to less than 1/10; infrequently - from more than 1/1000 to less than 1/100; seldom - from more than 1/10000 to less than 1/1000; very seldom - from less than 1/10000, including separate messages.

From the central nervous system: often - a headache, dizziness, increased fatigue, drowsiness; infrequently - an adynamy, a febricula, hypesthesias, paresthesias, peripheral neuropathy, a tremor, sleeplessness, lability of mood, unusual dreams, a hyperexcitability, a depression, uneasiness; very seldom - migraine, the increased sweating, apathy, agitation, an ataxy, amnesia.

From the alimentary system: often - nausea, abdominal pains; infrequently - vomiting, a lock or diarrhea, a meteorism, dyspepsia, anorexia, dryness of a mucous membrane of an oral cavity, thirst; seldom - a hyperplasia of gums, increase in appetite; very seldom - the pancreatitis, gastritis, jaundice (caused by a cholestasia), a hyperbilirubinemia, increase in activity of "hepatic" transaminases, hepatitis.

From cardiovascular system: often - heartbeat, peripheral hypostases (anklebones and feet), "inflows" of blood to face skin; infrequently - excessive decrease in the ABP; seldom - an asthma; very seldom - a syncope, a vasculitis, orthostatic hypotension, development or aggravation of a course of chronic heart failure, disturbance of a heart rhythm (including bradycardia, ventricular tachycardia and atrial fibrillation), a myocardial infarction, thorax pain.

From bodies of a hemopoiesis: very seldom - a Werlhof's disease, a leukopenia, thrombocytopenia.

From urinogenital system: infrequently - the speeded-up urination, an urodynia, a nocturia, impotence; very seldom - a dysuria, a polyuria.

From respiratory system: seldom - short wind, rhinitis; very seldom - cough.

From a musculoskeletal system: infrequently - muscular spasms, a mialgiya, an arthralgia, a dorsodynia, arthrosis; seldom - a myasthenia.

From integuments: seldom - dermatitis; very seldom - an alopecia, a xerodermia, cold sweat, disturbance of a xanthopathy.

Allergic reactions: skin itch, rash (including erythematic, makulopapulezny rash, small tortoiseshell), Quincke's disease, multiformny erythema.

Others: infrequently - a ring in ears, a diplopia, accommodation disturbance, a xerophthalmia, conjunctivitis, eye pain, a fever, nasal bleeding, a gynecomastia; very seldom - a parosmiya, a hyperglycemia.

At emergence of these or those adverse side reactions, as soon as possible see a doctor.

If any of the side effects specified in the instruction are aggravated, or you noticed any other side effects which are not specified in the instruction, report about it to the doctor.

Interaction with other medicines:

Amlodipin can safely be applied to therapy of arterial hypertension together with thiazide diuretics, alpha adrenoblockers, beta adrenoblockers or APF inhibitors. At patients with stable stenocardia амлодипин it is possible to combine with other anti-anginal means, for example, with nitrates of the prolonged or short action, beta adrenoblockers.

Unlike other BMKK of clinically significant interaction of an amlodipin (the II generation of BMKK) it was not revealed at combined use with non-steroidal anti-inflammatory drugs (NPVP) including with indometacin.

Strengthening of anti-anginal and hypotensive action of BMKK at combined use with thiazide and "loopback" diuretics, APF inhibitors, beta adrenoblockers and nitrates, and also strengthening of their hypotensive action at combined use with alfa1-adrenoblockers is possible.

Though when studying an amlodipin of negative inotropic effect usually did not observe, nevertheless, some BMKK can increase expressiveness of negative inotropic effect of the antiarrhytmic means causing lengthening of an interval of QT (for example, Amiodaronum and quinidine).

The single dose of 100 mg of a sildenafil at patients with essential hypertensia does not exert impact on parameters of pharmacokinetics of an amlodipin.

Repeated use of an amlodipin in a dose of 10 mg and an atorvastatina in a dose of 80 mg is not followed by considerable changes of indicators of pharmacokinetics of an atorvastatin.

Ethanol (the drinks containing alcohol): амлодипин at single and repeated use in a dose of 10 mg does not influence ethanol pharmacokinetics.

Antiviral means (ритонавир) increases plasma concentration of BMKK including an amlodipina.

Neuroleptics and изофлуран - strengthening of hypotensive action of derivatives of dihydropyridine.

Drugs of calcium can reduce effect of BMKK.

At combined use of an amlodipin with drugs of lithium strengthening of manifestation of a neurotoxicity (nausea, vomiting, diarrhea, an ataxy, a tremor, a sonitus) is possible.

Amlodipin does not change cyclosporine pharmacokinetics.

Also its renal clearance does not exert impact on concentration in blood serum of digoxin.

Has no significant effect on effect of warfarin (prothrombin time).

Cimetidinum does not influence pharmacokinetics of an amlodipin.

In the researches in vitro амлодипин does not influence linkng with proteins of a blood plasma of digoxin, Phenytoinum, warfarin and indometacin.

Grapefruit juice: the concomitant single dose of 240 mg of grapefruit juice and 10 mg of an amlodipin inside is not followed by essential change of pharmacokinetics of an amlodipin.

Aluminum - or magniysoderzhashchy antacids: their single dose has no significant effect on pharmacokinetics of an amlodipin.

If you accept other drugs, it is necessary to consult with the doctor.

Contraindications:

— hypersensitivity to an amlodipin, other derivatives of dihydropyridine and other components of drug;

— the expressed arterial hypotension (systolic the ABP less than 90 mm hg);

— unstable stenocardia (except for Printsmetal's stenocardia);

— clinically significant stenosis of an aorta;

— age up to 18 years (efficiency and safety are not established).

With care to apply at: abnormal liver functions, a sick sinus syndrome (the expressed bradycardia, tachycardia), chronic heart failure of not ischemic etiology of the III-IV functional class on classification of NYHA, arterial hypotension, an aortal stenosis, a mitral stenosis, a hypertrophic subaortic stenosis, an acute myocardial infarction (and within 1 month after a myocardial infarction), at advanced age. If at you one of the listed diseases, before administration of drug surely consult with the doctor.

Overdose:

Symptoms: the expressed decrease in the ABP with possible development of reflex tachycardia and an excessive peripheral vazodilatation (risk of development of the expressed and persistent arterial hypotension, including with development of shock and a lethal outcome).

Treatment: a gastric lavage, reception of absorbent carbon (especially in the first 2 h after overdose), maintenance of function of cardiovascular system, sublime position of the lower extremities, monitoring of indicators of cardiac performance and lungs, control of the volume of the circulating blood (VCB) and a diuresis. For recovery of a tone of vessels - use of vasoconstrictors (in the absence of contraindications to their use); for elimination of effects of blockade of calcium channels - intravenous administration of calcium of a gluconate. The hemodialysis is inefficient.

Storage conditions:

In the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children. A period of validity - 3 years. Not to use after the date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in strips, on 3 strips in a cardboard pack.