Amlodipin

General characteristics. Structure:

One tablet of 5 mg contains active agent: an amlodipina бесилат in terms of амлодипин — 5 mg;

Excipients: lactose (sugar milk) — 67,0 mg, potato starch — 6,5 mg, povidone (коллидон 25) — 2,85 mg, cellulose microcrystallic — 16,0 mg, magnesium stearate — 0,7 mg.

One tablet of 10 mg contains active agent: an amlodipina бесилат in terms of амлодипин — 10 mg;

Excipients: lactose (sugar milk) — 134,0 mg, potato starch — 13,0 mg, povidone (коллидон 25) — 5,7 mg, cellulose microcrystallic — 32,0 mg, magnesium stearate — 1,4 mg.

Pharmacological properties:

Pharmacodynamics. Derivative dihydropyridine — the blocker of "slow" calcium channels of the II generation, has anti-anginal and hypotensive effect. Contacting digidropiridino-vy 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 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 of stenocardia and consumption of nitroglycerine.
Renders long-term dozozavisimy hypotensive effect. Hypotensive action is caused by direct vazodilatiruyu-shchy impact on unstriated muscles of vessels. At arterial hypertension the single dose provides clinically significant lowering of arterial pressure (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 the coronary heart disease (CHD). 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, 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 hours, duration of effect is 24 hours.

Pharmacokinetics. After oral administration амлодипин it is slowly absorbed from digestive tract. Average absolute bioavailability makes 64%, the maximum concentration in blood serum is observed in 6-9 hours. Concentration of stable balance is reached after 7 days of therapy. Food does not influence absorption of an amlodipin. The average volume of distribution makes 21 l/kg of body weight that indicates that the most part of drug is in fabrics, and rather 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 extensive metabolism (90%) in a liver with formation of inactive metabolites, has effect of "the first passing" through a liver. Metabolites have no significant pharmacological activity.
After single oral administration the elimination half-life (T1/2) varies from 31 to 48 hours, at repeated purpose of T1D makes about 45 hours. About 60% of the dose accepted inside are excreted with urine preferential in the form of metabolites, 10% in not changed look, and 20-25% with a stake, and also with breast milk. 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 (T112 65 h) in comparison with young patients, however this difference has no clinical value. At patients with a liver failure lengthening of T1H is supposed, and at long appointment 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. Drug gets through a blood-brain barrier. At a hemodialysis is not removed.

Indications to use:

Arterial hypertension (monotherapy or in a combination with other anti-hypertensive means). 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 drug of 1 times a day. The dose as much as possible can be increased to 10 mg once in days. At arterial hypertension the maintenance dose can be 5 mg a day.

At an angina of exertion and vasospastic stenocardia — 5-10 mg a day, once. To thin patients, patients of low growth, elderly patients, the patient with an abnormal liver function as an antihypertensive appoint 2,5 mg in an initial dose; as antianginal-ny means — 5 mg.
Change of a dose at co-administration with thiazide diuretics, beta adrenoblockers and inhibitors of an angiotensin-converting enzyme (APF) 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 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 syndrome of "cancellation", before the termination of treatment gradual reduction of doses is recommended. Amlodipin does not influence plasma concentration To *, glucose, triglycerides, the general cholesterol, LPNP, uric acid, creatinine and nitrogen of uric acid.

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

Side effects:

- From cardiovascular system: heartbeat, an asthma, the expressed lowering of arterial pressure, a faint, a vasculitis, hypostases (puffiness of anklebones and feet), "inflows" of blood to the person, is rare — disturbances of a rhythm (bradycardia, ventricular tachycardia, an atrial flutter), thorax pain, orthostatic hypotension, is very rare — development or aggravation of heart failure, premature ventricular contraction, migraine.
- From the central nervous system: a headache, dizziness, fatigue, drowsiness, change of mood, a spasm, it is rare — a loss of consciousness, a hypesthesia, nervousness, paresthesias, a tremor, вертиго, an adynamy, an indisposition, sleeplessness, a depression, unusual dreams, it is very rare — an ataxy, apathy, agitation, amnesia.
- From the alimentary system: nausea, vomiting, pains in epigastriums, it is rare — the increase in level of "hepatic" transaminases and jaundice (caused by a cholestasia), pancreatitis, dryness in a mouth, a meteorism, a hyperplasia of gums, a lock or diarrhea, is very rare — gastritis, increase in appetite, anorexia, a hyperbilirubinemia.
- 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 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.
- From a musculoskeletal system: seldom — an arthralgia, arthrosis, a mialgiya (at prolonged use); very seldom — a myasthenia.
- Other: seldom — a gynecomastia, a polylithemia, increase/decrease in body weight, thrombocytopenia, a leukopenia, a hyperglycemia, a vision disorder, a diplopia, conjunctivitis, eye pain, a ring in ears, a dorsodynia, диспноэ, nasal bleeding, the increased sweating, thirst; very seldom — a cold clammy sweat, cough, rhinitis, a parosmiya, disturbance of flavoring feelings, accommodation disturbance, a xerophthalmia.

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 non-steroidal anti-inflammatory drugs, 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 адренобпокаторы, 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:

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

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

Overdose:

Symptoms: the expressed lowering of arterial pressure, tachycardia, an excessive peripheral vazodilatation.

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 a gluconate of calcium. The hemodialysis is not effective.

Storage conditions:

List B. In the dry, protected from light place, at a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets on 5 mg and 10 mg.
On 10, 30 tablets in a blister strip packaging. On 10, 20, 30, 40, 50 or 100 tablets in a container polymeric for medicines or a bottle from glass melt with the screwed plastic covers. One container (bottle) or 1,2,3,4,5, 6,8 or 10 blister strip packagings together with the application instruction place in a pack from a cardboard.
On 5, 10 or 20 containers (bottles) or on 20, 40, 60, 80 and 100 blister strip packagings together with application instructions place in a box from a cardboard (for hospitals).