AMLODIPIN-BIOKOM of 10 mg

General characteristics. Structure:

The operating component: an amlodipina безилат – 0,00694 g or 0,01389 g in terms of амлодипин – 0,0050 g or 0,0100 g

Excipients: lactoses monohydrate (sugar milk) – 0,07953 g or 0,11619 g, potato starch – 0,00058 g or 0,00084 g, starch prezhelatinizirovanny – 0,00895 g or 0,01308 g, magnesium stearate – 0,001 g or 0,0015 g, croscarmellose sodium (primelloza) – 0,003 g or 0,0045 g.

Pharmacological properties:

Pharmacodynamics. Derivative dihydropyridine - the blocker of "slow" calcium channels (BMKK) of the II generation, has anti-anginal and hypotensive effect. Contacting a S6 III and IV segment of domains of alfa1-subunit of a calcium channel of L-type, blocks calcium channels, reduces transmembrane transition ^{of Ca2 +} in a cell (more in smooth muscle cells of vessels, than in cardiomyocytes). Renders hypotensive and anti-anginal effect.

The mechanism of hypotensive action of an amlodipin is caused by the direct weakening impact on unstriated muscles of vessels.

Reduction of ischemia of a myocardium happens due to expansion of coronary and peripheral arteries and arterioles in not changed and in ischemic zones of a myocardium, decrease in the general peripheric vascular resistance, reduction of an afterload, the need of a myocardium for oxygen.

Increases intake of oxygen in a myocardium at patients with vasospastic stenocardia (Printsmetal's stenocardia); prevents development of the coronary spasm caused by smoking. At patients with stenocardia the single daily dose increases time of performance of an exercise stress, development of the next attack of stenocardia and depression of a segment of S-T detains (on 1 mm) at an exercise stress, reduces the frequency of attacks of 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 daily dose provides clinically significant lowering of arterial pressure (ABP) for 24 h (in position of the patient "lying" and "standing").

At the patients with diseases of cardiovascular system (including coronary atherosclerosis with defeat of one vessel and to a stenosis of the 3rd and more arteries, atherosclerosis of carotid arteries) who had the myocardial infarction (MI), chrezkozhny transluminal angioplasty of coronary arteries or patients with stenocardia. Use of an amlodipin warns a thickening erotic-medii of carotid arteries, reduces a lethality from IT, a stroke, transluminal angioplasty, aortocoronary shunting; leads to decrease in number of hospitalization concerning unstable stenocardia and progressing of the chronic heart failure (CHF); reduces the frequency of the interventions directed to recovery of a coronary blood-groove.

Does not increase risk of death or development of complications and lethal outcomes at sick HSN (the III-IV functional class on classification of the New York cardiological association (NYHA)) against the background of therapy by digoxin, diuretics and inhibitors of an angiotensin-converting enzyme (APF). Sick HSN (the III-IV functional class on NYHA classification) not ischemic etiology at use of an amlodipin have a probability of emergence of a fluid lungs.

Does not cause sharp decrease in the ABP, decrease in tolerance to an exercise stress, fraction of emission of the left ventricle (LV). Reduces LZh myocardium hypertrophy degree.

Does not exert impact on contractility and conductivity of a myocardium, does not cause reflex increase in heart rate, 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 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 %. The maximum concentration in blood (TCmax) at oral administration is reached in 6-12 h. At constant reception stationary concentration in blood (Css) is created in 7-8 days. Distribution volume - 21 l/kg. Communication with proteins of plasma - 90-97 %. Gets through a blood-brain barrier.

Intensively (90 %) it is metabolized in a liver with formation of inactive metabolites, has effect of "primary passing" through a liver. Time of half-decay _(T½) on average – 35 h. The general clearance - 500 ml/min.

_T½ patients with arterial hypertension have 48 h, at elderly patients increases to 65 h, at a liver failure - to 60 h, similar parameters of increase _T½ are observed also at heavy HSN, at a renal failure - does not change. At a hemodialysis is not removed.

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.

Indications to use:

Arterial hypertension (in monotherapy or in a combination with other anti-hypertensive means).

Stable angina of exertion and vasospastic stenocardia (in monotherapy or in a combination with other anti-anginal means).

Route of administration and doses:

Inside, once a day, washing down with a necessary amount of water (100 ml).

At arterial hypertension and stenocardia the initial dose makes 5 mg of 1 times a day. If necessary the daily dose can be increased to 10 mg, in one step.

At elderly patients

Amlodipin is recommended to apply in an average therapeutic dose, dose adjustment is not required.

At patients with an abnormal liver function

In spite of the fact that _Т½ Amlodipina, as well as all BMKK, increases at patients with an abnormal liver function, dose adjustment usually is not required (see the section "Special Instructions").

At patients with a renal failure

Amlodipin in usual doses is recommended to apply, however it is necessary to consider possible insignificant increase _Т½.

Dose adjustment at co-administration with thiazide diuretics, beta adrenoblockers and APF inhibitors is not required.

Features of use:

During therapy by drug by Amlodipin-Biok it is necessary to control the body weight and consumption of sodium, purpose of the corresponding diet is shown.

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

At patients of advanced age _T1/2 can increase and decrease clearance of drug. Change of doses is not required, but more careful observation of patients of this category is necessary.

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

Efficiency and safety of use of Amlodipin-Biokom at hypertensive crisis is not established.

Despite the absence of at BMKK of a syndrome of "cancellation", it is desirable to carry out by the termination of treatment by Amlodipinom-Biokom, gradually reducing a drug dose.

Influence on ability to control of motor transport and other difficult mechanisms.

Against the background of Amlodipin's reception any negative influence on ability to manage motor transport or other difficult mechanisms was not observed, however, owing to possible excessive decrease in the ABP, development of dizziness, drowsiness and other side reactions, it is necessary to be careful in the listed situations, especially in an initiation of treatment and at increase in a dose.

Side effects:

Frequency of the side reactions given below was defined according to the following (classification of World Health Organization): very often - more than 1/10, it is frequent - from more than 1/100 to less than 1/10, infrequently - from more than 1/1000 to less than 1/100, is rare - from more than 1/10000 to less than 1/1000, is very rare - from less than 1/10000, including separate messages.

From the central nervous system: often - a headache, dizziness, increased fatigue, drowsiness; infrequently – an adynamy, a febricula, hypesthesias, paresthesias, peripheral neuropathy, a tremor, sleeplessness, lability of mood, unusual dreams, a hyperexcitability, a depression, uneasiness; very seldom – migraine, the increased sweating, apathy, agitation, an ataxy, amnesia.

From the alimentary system: often - nausea, abdominal pains; infrequently – vomiting, a lock or diarrhea, a meteorism, dyspepsia, anorexia, dryness of a mucous membrane of an oral cavity, thirst; seldom – a hyperplasia of gums, increase in appetite; very seldom – the pancreatitis, gastritis, jaundice (caused by a cholestasia), a hyperbilirubinemia, increase in activity of "hepatic" transaminases, hepatitis.

From cardiovascular system: often - heartbeat, peripheral hypostases (anklebones and feet), "inflows" of blood to face skin; infrequently – excessive decrease in the ABP; very seldom – a syncope, an asthma, a vasculitis, orthostatic hypotension, development or aggravation of a current of HSN, disturbance of a heart rhythm (including bradycardia, ventricular tachycardia and atrial fibrillation), a myocardial infarction, thorax pain.

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

From urinogenital system: infrequently – the speeded-up urination, an urodynia, a nocturia, impotence; very seldom – a dysuria, a polyuria.

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

From a musculoskeletal system: infrequently – muscular spasms, a mialgiya, an arthralgia, a dorsodynia, arthrosis; seldom – a myasthenia.

From integuments: seldom – dermatitis; very seldom - an alopecia, a xerodermia, cold sweat, disturbance of a xanthopathy.

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

Others: infrequently – a ring in ears, a diplopia, accommodation disturbance, a xerophthalmia, conjunctivitis, eye pain, a fever, nasal bleeding, a gynecomastia; very seldom - a parosmiya, a hyperglycemia.

Interaction with other medicines:

Amlodipin can safely be applied to therapy of arterial hypertension together with thiazide diuretics, alpha adrenoblockers, beta adrenoblockers or APF inhibitors. At patients with stable stenocardia амлодипин it is possible to combine with other anti-anginal means, for example, with nitrates of the prolonged or short action, beta adrenoblockers.

Unlike other BMKK of clinically significant interaction of an amlodipin (the III generation of BMKK) it was not revealed at combined use with non-steroidal anti-inflammatory drugs including with indometacin.

Strengthening of anti-anginal and hypotensive action of BMKK at combined use with thiazide and "loopback" diuretics, APF inhibitors, beta adrenoblockers and nitrates, and also strengthening of their hypotensive action at combined use with alfa1-adrenoblockers, neuroleptics is possible.

Though when studying an amlodipin of negative inotropic effect usually did not observe, nevertheless, some BMKK can increase expressiveness of negative inotropic effect of the antiarrhytmic means causing lengthening of an interval of QT (for example, Amiodaronum and quinidine).

The single dose of 100 mg of a sildenafil at patients with essential hypertensia does not exert impact on parameters of pharmacokinetics of an amlodipin.

Repeated use of an amlodipin in a dose of 10 mg and an atorvastatina in a dose of 80 mg is not followed by considerable changes of indicators of pharmacokinetics of an atorvastatin.

Ethanol (the drinks containing alcohol): амлодипин at single and repeated use in a dose of 10 mg does not influence ethanol pharmacokinetics.

Antiviral means (ритонавир) increases plasma concentration of BMKK including an amlodipina.

Neuroleptics and изофлуран – strengthening of hypotensive action of derivatives of dihydropyridine.

Drugs of calcium can reduce effect of BMKK.

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

Amlodipin does not change cyclosporine pharmacokinetics.

Also its renal clearance does not exert impact on concentration in blood serum of digoxin.

Has no significant effect on effect of warfarin (prothrombin time).

Cimetidinum does not influence pharmacokinetics of an amlodipin.

In the researches in vitro амлодипин does not influence linkng with proteins of a blood plasma of digoxin, Phenytoinum, warfarin and indometacin.

Grapefruit juice: the concomitant single dose of 240 mg of grapefruit juice and 10 mg of an amlodipin inside is not followed by essential change of pharmacokinetics of an amlodipin.

Aluminum - or magniysoderzhashchy antacids: their single dose has no significant effect on pharmacokinetics of an amlodipin.

Contraindications:

- hypersensitivity to an amlodipin, other derivatives of dihydropyridine and other components of drug (monohydrate is a part of drug lactoses);

- the expressed arterial hypotension (systolic the ABP less than 90 mm hg);

- unstable stenocardia (except for Printsmetal's stenocardia);

- clinically significant stenosis of an aorta;

- age up to 18 years (efficiency and safety are not established);

- pregnancy and period of a lactation.

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, sublime position of the lower extremities, monitoring of indicators of cardiac performance and lungs, control of volume of the circulating blood and a diuresis. For recovery of a tone of vessels - use of vasoconstrictors (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 inefficient.

Storage conditions:

In the dry, protected from light place at a temperature not over 25 ºС. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets on 5 mg and 10 mg.

On 10 tablets in a blister strip packaging. On 1, 2, 3, 4 or 5 blister strip packagings together with the instruction on a medical use in a pack cardboard.