Amlodipin

General characteristics. Structure:

Active agent: an amlodipina бесилат in terms of амлодипин-5 mg or 10 mg; excipients: cellulose microcrystallic, calcium hydrophosphate anhydrous, sodium carboxymethylcellulose (karmeloz of sodium), magnesium стерат.

Pharmacological properties:

Pharmacodynamics. 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 (to a large extent in smooth muscle cells of vessels, than and 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 peripheral 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 frequencies)' attacks of stenocardia and consumption of nitroglycerine. Renders long-term dozozavisimy hypotensive effect. Hypotensive action is caused by direct vazodilatiruyushy 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. Equilibrium concentration 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 (Ti/2) varies from 31 to 48 hours, at repeated purpose of Ti/2 makes about 45 hours. About 60% of the dose accepted inside are excreted with urine preferential in the form of metabolikt, 10% in an invariable 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 (Ti/2 65 of the h) in comparison with young patients, however this difference has no clinical value. Patients with a liver failure have a lengthening of Ti/2 and at long appointment cumulation of drug in an organism will be higher (Ti/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 (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 days. The dose as much as possible can life is increased to 10 mg is single in days. At arterial hypertension the maintenance dose can life in days. At an angina of exertion (vazopastichesky stenocardia) - 5-10 mg a day, once.  Change of a dose priodnovremenny appointment with thiazide diuretics, beta адреноблакотарами and ingbitor the angiotensin-the turning enzyme (ATE) 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 of K+, glucose, triglycerides, the general cholesterol, LPNP. uric acid, creatinine and nitrogen of uric acid. Influence on ability to driving and the mekhanizmamiyena was messages on influence of an amlodipin on driving or work with mechanisms. Nevertheless, some patients preferential treatment can have in the beginning a drowsiness and dizziness. At their emergence the patient has to refrain from 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), pain to a thorax, 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, changes of mood, a spasm, it is rare - a loss of consciousness, a hypesthesia, nervousness, paresthesias, a tremor, twirl го, 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 холестазм), pancreatitis, dryness in a mouth, a meteorism, a hyperplasia of gums, a lock or diarrhea, very seldom gastritis, increase in appetite.

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 discolorations.

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 long use); very seldom - a myasthenia.

Others: seldom - a gynecomastia, a hyperuricemia, 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 paroyemiya, disturbance of flavoring feelings, accommodation disturbance; 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 adrenoblockers, verapamil, APF inhibitors and nitrates strengthen anti-anginal and hypotensive effects. Amiodaronum, quinidine, an alpha 1 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. Tsimstidin 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; expressions arterial hypotension; collapse, cardiogenic shock; unstable stenocardia (except for Printsmetal's stenocardia) pregnancy the lactation period; age up to 18 years (efficiency and safety are not established). With care: an abnormal liver function, a 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 vazodilataniya. 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. To store in dry, protected from light and the place, unavailable to children, at a temperature not above 25 °C.

Issue conditions:

According to the recipe

Packaging:

Tablets on 5 and 10 mg. On 10, 14 tablets in a blister strip packaging from a film of the polyvinyl chloride and aluminum foil varnished. On 1,2,3 blister strip packagings on 14 tablets together with the application instruction place in a pack from a cardboard. On 50 or 100 tablets in bank for packaging of medicines from polypropylene or to bank from polyethylene of high pressure or from polyethylene of low pressure, corked by a cover of polypropylene or polyethylene. Each can together with the application instruction will prevent in a pack for a retail container of subgroups chromic or chrome - ersatz.