Amlodipin таб. 0.01; 0,005 No. 30

General characteristics. Structure:

Active ingredient: амлодипин; 1 tablet contains an amlodipin of 5 mg or 10 mg;
Excipients: lactose, cellulose microcrystallic, sodium of a kroskarmelloz, gipromelloz, povidone 25, magnesium stearate, silicon dioxide, E 132 indigo carmine.

Pharmacological properties:

Pharmacodynamics. Amlodipin is the antagonist of calcium (a blocker of slow calcium channels) who blocks receipt of calcium ions through membranes in cells of unstriated muscles of a myocardium and vessels. The mechanism of hypotensive action of an amlodipin is caused by direct influence on unstriated muscles of vessels.

The anti-anginal effect of Amlodipin is implemented in the next two ways:

1. Amlodipin expands peripheral arterioles and thus reduces OPSS (afterload). As ChSS practically does not change, decrease in load of heart leads to decrease in consumption of energy and need of a myocardium for oxygen.

2. Amlodipin also promotes expansion of coronary arterioles both in not changed, and in ischemic zones of a myocardium. Such dilatation increases intake of oxygen to a myocardium at patients with vasospastic stenocardia (Printsmetal's stenocardia or alternative stenocardia) and prevents development of coronary vasoconstriction.

At patients with arterial hypertension the single dose of an amlodipin provides clinically significant decrease in the ABP for 24 h as in a prone position, and standing. Thanks to the slow beginning of action амлодипин does not cause acute arterial hypotension.

At patients with stenocardia амлодипин promotes increase in physical effeciency (extends time of performance of an exercise stress, development of an attack of stenocardia and oppression of a segment of ST at loadings detains), reduces the frequency of attacks of stenocardia and the need for the use of Tabulettaes Nitroglycerini.

The researches in vitro showed that about 97,5% of an amlodipin contact proteins of a blood plasma.

Amlodipin has no adverse influence on a metabolism and lipids of a blood plasma therefore he is suitable for treatment of patients with bronchial asthma, a diabetes mellitus and gout.

Geodynamic researches and controlled clinical tests at patients with heart failure of the II-III functional classes on classification of the New York association of heart (NYHA) showed what амлодипин does not cause deterioration in their state by such criteria as tolerance to an exercise stress, fraction of emission of a left ventricle and clinical symptomatology.

In placebo - controlled researches it is shown that use of an amlodipin does not lead to increase in risk of a lethality or the combined lethality indicator at patients with heart failure of the III-IV classes (NYHA) receiving digoxin, diuretics and APF inhibitors.

Pharmacokinetics. After intake in therapeutic doses амлодипин it is well soaked up, reaching the maximum concentration in blood in 6 - 12 hours at patients as average, and advanced age. Absolute bioavailability reaches 64 - 80%. The volume of distribution makes about 21 l/kg. Meal does not influence absorption of an amlodipin.

Plasma elimination half-life of blood makes about 35 - 50 hours that allows to appoint drug once a day. Steady equilibrium concentration in a blood plasma is reached in 7 - 8 days of regular use of an amlodipin.

Amlodipin is transformed in a liver with formation of inactive metabolites. It is removed with urine: 10% of a dose - in not changed look, 60% - in the form of metabolites.

At elderly patients and patients with congestive heart failure the tendency to decrease in clearance of an amlodipin is noted that leads to increase in AUC (the area under a curve "concentration / time") and the period напиввидення drug.

Indications to use:

Arterial hypertension (as means of the first row). Drug can be used for monotherapy of hypertensia at most of patients, in need of it it is possible to appoint also in combination with thiazide diuretics, α-adrenoceptors, β-adrenoceptors and APF inhibitors.

Coronary heart disease, including it is caused as organic by impassability (stable stenocardia), and a spasm or narrowing of coronary arteries (Printsmetal's stenocardia or alternative stenocardia). Drug can be used and when the clinical picture allows to assume only existence of a vasospasm or vasoconstriction though presence of the last it is definitely not established. Amlodipin it is possible to appoint as means of monotherapy or in combination with other anti-anginal drugs.

Route of administration and doses:

At arterial hypertension and stenocardia the usual initial dose of an amlodipin makes 5 mg once a day. Depending on individual reaction of the patient, the dose can be increased to the maximum, equal 10 mg.

At treatment amlodipiny it is necessary to exercise daily control of arterial pressure.

When carrying out a combination therapy the dose of an amlodipin does not need to be changed.

Features of use:

Use for patients with heart failure.

At use of an amlodipin for treatment of patients with heart failure of the III-IV degree (on NYHA classification) increase in number of cases of a fluid lungs is noted.

Use for patients with an abnormal liver function

The drug elimination half-life, as well as other antagonists of calcium, increases at patients with an abnormal liver function, however any recommendations concerning correction of doses of drug are not developed yet. For this reason to use drug at such patients follows with extra care and only under observation of the doctor.

Use for patients with a renal failure

At this category of patients Amlodipin apply in usual doses. Change of concentration of an amlodipin in a blood plasma does not correlate with degree of a renal failure. Amlodipin does not leave during dialysis.

Use for patients of advanced age

At the same doses patients of both summer, and younger age equally well transfer Amlodipin. Drug contains lactose that should be considered the patient with a hereditary lactose intolerance.
Influence on ability to manage motor transport or other mechanisms

Amlodipin's use demonstrates that deterioration in ability to drive the car and to work with mechanisms, connected with administration of drug, is improbable.

Period of pregnancy and feeding by a breast. Degree of safety of use of Amlodipin for women during pregnancy and feeding by a breast is not established. When studying influence of drug on reproductive function at animals toxicity signs, except for a delay of childbirth and increase in duration of pains at rats were not revealed at introduction of an amlodipin in doses, by 50 times exceeded most recommended for the person. Therefore, it is recommended to use drug during pregnancy only when there is no safer alternative, and the risk connected with a disease exceeds possible harm of treatment for mother and a fruit.

Children. Safety and efficiency of use of an amlodipin for children are not established therefore drug is not used in pediatric practice.

Side effects:

From cardiovascular system: often - peripheral hypostases (anklebones and feet), the strengthened heartbeat, sometimes - the expressed decrease in the ABP, orthostatic hypotension, a vasculitis, is rare - development or increase in heart failure, is very rare - disturbances of a heart rhythm (including bradycardia, ventricular tachycardia and atrial fibrillation), a myocardial infarction, thorax pain, migraine.

From a musculoskeletal system: sometimes - an arthralgia, myotonia, a hyper tone of muscles, a mialgiya, a dorsodynia, arthrosis; seldom - a myasthenia.

From TsNS and peripheral nervous system: often - feeling of heat and "inflows" of blood to face skin, increased fatigue, dizziness, a headache, drowsiness, sometimes - the indisposition, a syncope, the increased perspiration, an adynamy, a hypesthesia, paresthesias, peripheral neuropathy, a tremor, sleeplessness, lability of mood, unusual dreams, nervousness, a depression, alarm, is rare - spasms, apathy, agitation; very seldom - an ataxy, amnesia.

From the alimentary system: often - an abdominal pain, nausea, sometimes - vomiting, a lock, a meteorism, dyspepsia, diarrhea, anorexia, dryness in a mouth, thirst, it is rare - a hyperplasia of gums, increase in appetite, is very rare - gastritis, pancreatitis, a hyperbilirubinemia, jaundice (usually cholestatic), increase in activity of hepatic transaminases, hepatitis.

From the hemopoietic system: very seldom - a Werlhof's disease, a leukopenia, thrombocytopenia.

From a metabolism: very seldom - a hyperglycemia.

From respiratory system: sometimes - suffocation, rhinitis, is very rare - cough.

From an urinary system: sometimes - increase in frequency of an urination, an urodynia, a nocturia, impotence, is very rare - a dysuria, a polyuria.

Allergic reactions: sometimes - a skin itch, rash, it is very rare - a Quincke's disease, a multiformny erythema, a small tortoiseshell.

Others: sometimes - 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, taste change, a tremor, nasal bleeding, it is rare - dermatitis, is very rare - a parosmiya, a xerodermia, cold sweat, disturbance of a xanthopathy.

Interaction with other medicines:

Amlodipin is safe at use with thiazide diuretics, α-adrenoceptors, β-adrenoceptors, APF inhibitors, nitrates of long action, nitroglycerine which was applied sublingual, from a nesteroinima by antiinflammatory drugs and peroral hypoglycemic means.

Results of the researches in vitro with use of a blood plasma of the person demonstrate that drug does not influence linkng with proteins of such drugs as digoxin, Phenytoinum, warfarin and indometacin.

Influence of drugs on pharmacokinetics of an amlodipin. Combined use of an amlodipin and Cimetidinum does not change pharmacokinetics of an amlodipin.

Simultaneous use of 240 ml of grapefruit juice with a single peroral dose of an amlodipin of 10 mg at 20 healthy volunteers did not change pharmacokinetics of an amlodipin.

Combined use aluminum / magnesian antacids with a single dose of an amlodipin did not influence pharmacokinetics of an amlodipin.

The single dose of a sildenafil of 100 mg at patients essential AG did not influence pharmacokinetics of an amlodipin. At the combined use of an amlodipin and sildenafil each of drugs independently from each other showed hypotensive effect.

Influence of an amlodipin on pharmacokinetics of other drugs. Combined repeated use of 10 mg of an amlodipin and 80 mg of an atorvastatin did not influence equilibrium pharmacokinetic parameters of an atorvastatin.

Simultaneous use of an amlodipin and digoxin for healthy volunteers does not change the level of the last in blood serum and its renal clearance.

Single and reusable doses of an amlodipin of 10 mg did not change ethanol pharmacokinetics.

Amlodipin practically does not influence pharmacokinetics of cyclosporine and does not change influence of warfarin on a prothrombin time.

Contraindications:

Heavy arterial hypotension, aortal stenosis, unstable stenocardia (except for Printsmetal's stenocardia). Amlodipin is contraindicated to patients with the revealed individual hypersensitivity to dihydropyridines or to an amlodipin or any other component of drug. Cardiogenic shock.

Overdose:

Experience of treatment of a deliberate amlodipin of overdose at the person is limited. In certain cases there can be useful a gastric lavage. The existing data give the grounds to believe that considerable the overdose can lead to an excessive peripheral vazodilatation with the subsequent noticeable and, perhaps, long decrease in the ABP. Clinically significant arterial hypotension caused by drug overdose demands holding the active actions directed to maintenance of functions of cardiovascular system including monitoring of indicators of cardiac performance and lungs, the raised position of extremities, control of volume of the circulating blood, and a diuresis. For recovery of a tone of vessels and arterial pressure there can be useful a use vascular narrowing drug if there are no contraindications for its appointment. For elimination of effects of blockade of calcium channels there can be useful an introduction of a gluconate of calcium. As амлодипин substantially contacts proteins, efficiency of dialysis is improbable

Storage conditions:

In the dry, protected from light place at a temperature not higher than 30 S. Hranit in the place, unavailable to children. A period of validity - 3 years.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets a dosage of 5 mg and 10 mg in the blister. 3 blisters in a pack from a cardboard.