Amlodipin

General characteristics. Structure:

Active agent: амлодипин (in the form of a bezilat) 10 mg; 5 mg.

Excipients: cellulose silicate microcrystallic, starch prezhelatinizirovanny, magnesium stearate.

Pharmacological properties:

Derivative dihydropyridine - the blocker of slow calcium channels of the II generation, has anti-anginal and hypotensive effect. Contacting dihydropyridinic receptors, 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, reduces preload of heart, reduces the need of a myocardium for oxygen. Expanding the main 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 development of a konstriktion of coronary arteries (including caused by smoking). At patients with stenocardia the single daily dose increases time of performance of an exercise stress, slows down development of stenocardia and ischemic depression of a segment of ST, reduces the frequency of attacks
stenocardia and consumption of nitroglycerine.
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). Does not cause sharp decrease in the ABP, decrease in tolerance to an exercise stress, fraction of emission of a left ventricle. Reduces degree of a hypertrophy of a myocardium of a left ventricle, has anti-atherosclerotic and cardiotyre-tread effect at coronary heart disease.
Does not exert impact on contractility and conductivity of a myocardium, does not cause reflex increase in ChSS, slows down aggregation of thrombocytes, raises a glomerular filtration rate, possesses a weak natriuretic effect. At a diabetic nephropathy does not increase expressiveness of a microalbuminuria. Does not exert adverse impacts on a metabolism and lipids of a blood plasma. Time of approach of effect - 2-4 h; duration - 24 h.

Pharmacokinetics. Absorption - slow, does not depend on meal, makes about 90%, bioavailability - 60-65%. Cmax in blood serum at intake is 6-12 h. Concentration of stable balance is reached after 7 days of therapy. Food does not influence absorption of an amlodipin. Average Vd - 21 l/kg that indicates that the most part of drug is in fabrics, and rather smaller - in blood. Communication with proteins of a blood plasma - 90-97%.
Intensively (90%) it is metabolized in a liver with formation of inactive metabolites, has effect of the first passing through a liver. Metabolites have no significant pharmacological activity. T1/2 averages - 35 h. The general clearance - 500 ml/min. It is removed by kidneys - 60% in the form of metabolites, 10% in not changed look; with bile and through intestines - 20-25% in the form of metabolites, and also with breast milk.
T1/2 at patients with arterial hypertension - 48 h.
At elderly patients (65 years are more senior) removal of an amlodipin is slowed down (T1/2 - 65 h) in comparison with young patients, however this difference has no clinical value.
At patients with a liver failure lengthening of T1/2 is supposed, and at prolonged use accumulation 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. 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 medicines);
— angina of exertion;
— vasospastic stenocardia (Printsmetal's stenocardia).

Route of administration and doses:

Inside, the initial dose for treatment of arterial hypertension and stenocardia makes 5 mg of 1 time/days with gradual increase within 7-14 days up to 10 mg/days, once. The maximum daily dose makes 10 mg. At arterial hypertension a maintenance dose - 5 mg/days.
At an angina of exertion and vasospastic stenocardia - 5-10 mg/days, once.
Change of a dose at co-administration with thiazide diuretics, beta adrenoblockers and APF inhibitors is not required.
Change of a dose is not required from patients with a renal failure.

Features of use:

During treatment control of body weight and consumption of sodium, purpose of the corresponding diet is necessary.

Maintenance of hygiene of teeth and frequentation of the stomatologist is necessary (for prevention of morbidity, bleeding and a hyperplasia of gums).

The dosing mode for elderly people same, as well as for patients of other age groups.

At increase in a dose careful observation of elderly patients is necessary.

Despite the absence of at blockers of slow calcium channels of a withdrawal, before the termination of treatment gradual reduction of doses is recommended.

Amlodipin does not influence plasma potassium concentrations, glucose, triglycerides, the general cholesterol, lipoproteids of low density, uric acid, creatinine and an urea nitrogen.

Influence on ability to driving of motor transport and to control of mechanisms

There were no messages on influence of an amlodipin on driving or work with mechanisms. Nevertheless, at some patients, it is preferential in an initiation of treatment, there can be a drowsiness and dizziness. At emergence the patient has to observe special precautionary measures during the driving and work with mechanisms.

Side effects:

From TsNS: headache, dizziness, fatigue, drowsiness, change of mood, spasm; seldom - a loss of consciousness, a hypesthesia, paresthesias, a tremor, вертиго, an adynamy, an indisposition, sleeplessness, nervousness, a depression, extraordinary dreams; very seldom - an ataxy, apathy, agitation, amnesia, migraine.

From the alimentary system: the nausea, an abdominal pain, increase in activity of hepatic transaminases and jaundice (caused by a cholestasia); seldom - dryness in a mouth, anorexia, vomiting, a lock or diarrhea, dyspepsia, a meteorism, a hyperplasia of gums; very seldom - gastritis, increase in appetite, pancreatitis.

From cardiovascular system: heartbeat, hypostases (puffiness of anklebones and feet), the expressed decrease in the ABP, an asthma, a syncope, a vasculitis, rushes of blood to the person; seldom - disturbances of a rhythm (bradycardia, ventricular tachycardia, an atrial flutter), thorax pain, orthostatic hypotension; very seldom - development or aggravation of heart failure, premature ventricular contraction.

From urinogenital system: seldom - a pollakiuria, painful desires on an urination, a nocturia, disturbance of sexual function (including decrease in a potentiality); very seldom - a dysuria, a polyuria.

From a bone myshechchnoy of system: seldom - an arthralgia, arthrosis, a mialgiya (at prolonged use); very seldom - a myasthenia.

From integuments: very seldom - a xerodermia, an alopecia, dermatitis, a purpura, skin discoloration.

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

Others: seldom - a vision disorder, conjunctivitis, a diplopia, eye pain, accommodation disturbance, a xerophthalmia, a ring in ears, a gynecomastia, a dorsodynia, feeling of heat and rushes of blood to the person, a fever, increase/decrease in body weight, thrombocytopenia, a leukopenia, a hyperglycemia, диспноэ, nasal bleeding, the increased sweating, thirst; very seldom - a cold clammy sweat, cough, rhinitis, a parosmiya, disturbance of flavoring feelings, a hyperglycemia.

Interaction with other medicines:

Inhibitors of a microsomal oxidation increase concentration of an amlodipin in a blood plasma, strengthening risk of development of side effects, and inductors of microsomal enzymes of a liver reduce.

Hypotensive effect NPVP, especially indometacin, (a delay of sodium and blockade of synthesis of prostaglandins kidneys), alpha адреностимуляторы weaken, estrogen (a sodium delay), sympathomimetics.

Thiazide and "loopback" diuretics, beta adrenoblockers, verapamil, APF inhibitors and nitrates strengthen anti-anginal and hypotensive effects.

Amiodaronum, quinidine, alfa1-adrenoblockers, antipsychotic medicines (neuroleptics) and blockers of slow calcium channels can strengthen hypotensive action.

Does not exert impact on pharmacokinetic parameters of digoxin and warfarin. Cimetidinum does not influence pharmacokinetics of an amlodipin.

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

Drugs of calcium can reduce effect of blockers of slow calcium channels.

The procaineamide, quinidine and other medicines causing lengthening of an interval of QT strengthen a negative inotropic effect and can increase risk of considerable lengthening of an interval of QT.

Grapefruit juice can reduce concentration of an amlodipin in a blood plasma, however this decrease so is not enough that significantly does not change action of an amlodipin.

Contraindications:

— the expressed arterial hypotension;
— collapse;
— cardiogenic shock;
— unstable stenocardia (except for Printsmetal's stenocardia);
— pregnancy;
— lactation period;
— age up to 18 years (efficiency and safety are not established);
— hypersensitivity to an amlodipin and other derivatives of dihydropyridine.

Sostorozhnost: arterial hypotension, an aortal stenosis, chronic heart failure in a decompensation stage, soft or moderate degree of arterial hypotension, an aortal stenosis, a mitral stenosis, a liver failure, an acute myocardial infarction (and within 1 month after), advanced age, a hypertrophic subaortic stenosis, a sick sinus syndrome (the expressed bradycardia, tachycardia), a diabetes mellitus, disturbance of a lipidic profile.

Use at pregnancy and feeding by a breast
Pregnancy and the period of a lactation - efficiency and safety are not established.
Use at renal failures
Change of a dose is not required from patients with a renal failure.

Use for elderly patients
The dosing mode for elderly people same, as well as for patients of other age groups.
At increase in a dose careful observation of elderly patients is necessary.

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

Overdose:

Symptoms: the expressed decrease in the ABP, an excessive peripheral vazodilatation, tachycardia.

Treatment: a gastric lavage, purpose of absorbent carbon, maintenance of function of cardiovascular system, control of indicators of function of heart and lungs, sublime position of extremities, control of volume of the circulating blood and a diuresis. For recovery of a tone of vessels - use of vasoconstrictive drugs (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:

To store in the unavailable to children, dry, protected from light place, at a temperature from 15 °C to 25 °C.

Issue conditions:

According to the recipe

Packaging:

Tablets of 10 mg: 20 pieces.

Tablets of 5 mg: 20 pieces.