Amlodipin

General characteristics. Structure:

Active agent: an amlodipina бесилат in terms of амлодипин 5 mg and 10 mg;

excipients: calcium stearate, potato starch, lactose (sugar milk), magnesium stearate, cellulose microcrystallic.

Description: Tablets of white or almost white color, ploskotsilindrichesky, with risky and a facet.

Pharmacological properties:

Pharmacodynamics. Amlodipin — derivative dihydropyridine — a blocker of "slow" calcium channels (BMKK) of the II generation, has anti-anginal and hypotensive effect. Contacting dihydropyridinic receptors, blocks calcium channels, reduces transmembrane transition of ions. calcium in 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, the need of a myocardium for oxygen. Expands 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 spasm of coronary arteries (including caused by smoking). At patients with stenocardia the single daily dose increases tolerance to an exercise stress, development of the next attack of stenocardia and "ischemic" depression of a segment of ST detains; reduces the frequency of attacks of stenocardia and consumption of nitroglycerine.

Amlodipin renders long-term dozozavisimy hypotensive effect which is caused by direct vazodilatiruyushy impact on unstriated muscles of vessels. At arterial hypertension the single daily dose of an amlodipin provides to clinically significant lowering of arterial pressure (ABP) for 24 hours (in position of the patient "lying" and "standing").

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, 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 impact on a metabolism and concentration of lipids of a blood plasma. Time of approach of therapeutic effect — 2–4 hours, duration — 24 hours.

Pharmacokinetics. After intake амлодипин it is slowly absorbed from digestive tract. Meal does not influence absorption of an amlodipin. Average absolute bioavailability makes 64%. The maximum concentration in blood serum is observed in 6–9 hours. Equilibrium concentration is reached after 7–8 days of therapy. Communication with proteins of a blood plasma makes 95%. The average volume of distribution — 21 l/kg of body weight. Amlodipin is exposed to slow, but active metabolism (90 - 97%) in a liver in the absence of significant effect of "the first passing". Metabolites have no significant pharmacological activity.

The elimination half-life (T1/2) averages — 35 hours. T1/2 at patients with arterial hypertension — 48 hours, at elderly patients increases till 65 o'clock, at a liver failure — till 60 o'clock, similar parameters of increase T1/2 are observed at heavy chronic heart failure, at a renal failure — does not change.

About 60% of the dose accepted inside are removed by kidneys preferential in the form of metabolites, 10% in not changed look, 20–25% — with bile and through intestines in the form of metabolites, and also with breast milk.

The general clearance of an amlodipin makes 0,116 ml / with/kg (7мл/мин/кг, 0,42 l/h/kg).

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

Indications to use:

- arterial hypertension (monotherapy or in a combination with other anti-hypertensive means);
- a stable angina of exertion and Printsmetal's stenocardia (monotherapy or in a combination with other anti-anginal means).

Route of administration and doses:

Inside, irrespective of meal.

For treatment of arterial hypertension and prevention of attacks of an angina of exertion and vasospastic stenocardia the initial dose of Amlodipin makes 5 mg of 1 times a day. If necessary the daily dose can be increased to maximum — 10 mg (1 times a day).

The patient with an abnormal liver function as an antihypertensive Amlodipin appoint with care, in an initial dose of 2,5 mg (1/2 tablets on 5 mg), as antiangialny means — 5 mg.

At patients of advanced age T1/2 can increase and decrease the clearance of creatinine (CC). Change of doses is not required, but more careful observation of patients is necessary.

Change of a dose at co-administration with thiazide diuretics is not required, to beta adrenoblockers and inhibitors of an angiotensin-converting enzyme (APF). Change of a dose is not required from patients with a renal failure.

Features of use:

During treatment by Amlodipin control of body weight of patients and amount of the sodium salt consumed by them is necessary; the corresponding low-salt diet is appointed.

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

The mode of dosing of Amlodipin at elderly patients is similar to that at sick other age groups. At increase in a dose careful observation of elderly patients is necessary.

Despite the lack of a syndrome of "cancellation" at BMKK, before the termination of treatment gradual reduction of doses is recommended.

Amlodipin does not influence plasma concentration in blood of potassium ions, glucose, triglycerides, the general cholesterol, lipoproteins of low density, uric acid, creatinine and an urea nitrogen.

It is necessary to avoid sharp drug withdrawal because of risk of deterioration in a course of stenocardia.

Drug tablets Amlodipin are not recommended at hypertensive crisis.

To patients of low growth and patients with the expressed abnormal liver functions the smaller dose can be required by patients with small body weight.

Influence on ability to driving of motor transport and to control of mechanisms
There were no messages on Amlodipin's influence on control of motor transport or work with mechanisms. Nevertheless, at some patients, it is preferential in an initiation of treatment, there can be a drowsiness and dizziness. At their emergence it is necessary to be careful during the driving of motor transport and occupation potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

From cardiovascular system: often — heartbeat, peripheral hypostases (puffiness of anklebones and feet), infrequently — excessive decrease in the ABP, orthostatic hypotension, a vasculitis; seldom — development or aggravation of chronic heart failure; very seldom — disturbances of a rhythm (bradycardia, ventricular tachycardia, atrial fibrillation), a myocardial infarction, thorax pain, migraine.

From the central nervous system: often — a headache, dizziness, increased fatigue; infrequently. - indisposition, syncope, adynamy, hypesthesia, paresthesias, peripheral neuropathy, tremor, sleeplessness, emotional lability, unusual dreams, nervousness, depression, alarm; seldom — spasms, apathy, agitation; very seldom — an ataxy, amnesia.

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

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

From a digestive tract: often — nausea, abdominal pain; infrequently — vomiting, change of the mode of defecation (including a lock, a meteorism), dyspepsia, diarrhea, anorexia, dryness of a mucous membrane of an oral cavity, thirst; seldom — a hyperplasia of gums, increase in appetite; very seldom — gastritis, pancreatitis, a hyperbilirubinemia, jaundice (usually cholestatic), increase in activity of "hepatic" transaminases, hepatitis.

From urinogenital system: infrequently — a pollakiuria, painful desires on an urination, a nocturia, impotence; very seldom — a dysuria, a polyuria.

From integuments: seldom — the increased sweating, is very rare - a cold clammy sweat, a xerodermia, an alopecia, dermatitis, a purpura, skin discoloration.

Allergic reactions: infrequently — a skin itch, rash; very seldom — a Quincke's disease, a multiformny erythema, a small tortoiseshell.

From a musculoskeletal system: infrequently — an arthralgia, myotonia, arthrosis, a mialgiya (at prolonged use), a dorsodynia; seldom — a myasthenia.

Others: infrequently — an alopecia, a ring in ears, a gynecomastia, increase/decrease in body weight, a vision disorder, a diplopia, accommodation disturbance, a xerophthalmia, conjunctivitis, eye pain, a food faddism, a fever, nasal bleeding, the increased sweating; seldom — dermatitis; very seldom — a cold clammy sweat, a parosmiya, disturbance of a xanthopathy, a hyperglycemia.

Interaction with other medicines:

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

Unlike other BMKK, at an amlodipin clinically significant interaction with non-steroidal anti-inflammatory drugs, especially with indometacin is not noted.

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

Amiodaronum, quinidine, alfa1-adrenoblockers, antipsychotic means (neuroleptics) and изофлуран can strengthen hypotensive action of an amlodipin.

Drugs of calcium can reduce effect of BMKK.

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

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

Antiviral means (ритонавир) promote increase in concentration of BMKK (including an amlodipina) in a blood plasma.

Contraindications:

- hypersensitivity to an amlodipin, other derivatives of dihydropyridine, other components of drug;
- the expressed arterial hypotension (systolic the ABP less than 90 mm of mercury.);
- collapse;
- cardiogenic shock;
- unstable stenocardia (except for Printsmetal's stenocardia);
- the expressed aortal stenosis;
- age up to 18 years (efficiency and safety are not established);
- lactose intolerance, deficit of lactase or glyukozo-galaktozny malabsorption;
- pregnancy;
- lactation period.

With care: an abnormal liver function, a sick sinus syndrome (the expressed bradycardia, tachycardia), chronic heart failure of not ischemic etiology of the III-IV functional class on NYHA classifications, an aortal stenosis, a mitral stenosis, a hypertrophic subaortic stenosis, an acute myocardial infarction (and within 1 month after), advanced age.

Use at pregnancy and in the period of a lactation
Teratogenecity of an amlodipin in a research on animals was not revealed, however there is no clinical experience of its use at pregnancy and in the period of a lactation. Therefore амлодипин it is not necessary to appoint pregnant and in the period of a lactation, and also to women of childbearing age if they do not use reliable methods of contraception.

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, purpose of absorbent carbon (especially in the first 2 hours after overdose), maintenance of function of cardiovascular system, control of indicators of function of heart and lungs, a pose of Trendelenburga, 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 the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity: 3 years. Not to apply after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets on 5 mg and 10 mg.

On 10 or 30 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished. On 1, 2, 3, 6, 9 blister strip packagings on 10 tablets or on 1, 2, 3, 4 blister strip packagings on 30 tablets together with the application instruction place in a pack from a cardboard.