Amlorus

General characteristics. Structure:

Tablets of white or almost white color, ploskotsilindrichesky, with a facet, existence of a mramornost is allowed.

Active ingredient: амлодипин (in the form of a bezilat) 2.5 mg

Excipients: lactoses monohydrate - 45.83 mg, cellulose microcrystallic - 45.7 mg, кросповидон - 1 mg, silicon dioxide colloid (aerosil) - 0.5 mg, talc - 2.5 mg, calcium stearate - 1 mg.

Tablets of white or almost white color, ploskotsilindrichesky, with a facet, existence of a mramornost is allowed.

Active ingredient: амлодипин (in the form of a bezilat) 5 mg

Excipients: lactoses monohydrate - 63.17 mg, cellulose microcrystallic - 62.9 mg, кросповидон - 1.4 mg, silicon dioxide colloid (aerosil) - 0.7 mg, talc - 3.5 mg, calcium stearate - 1.4 mg.

Tablets of white or almost white color, ploskotsilindrichesky, with a facet, existence of a mramornost is allowed.

Active ingredient: амлодипин (in the form of a bezilat) 10 mg

Excipients: lactoses monohydrate - 88.34 mg, cellulose microcrystallic - 87.8 mg, кросповидон - 2 mg, silicon dioxide colloid (aerosil) - 1 mg, talc - 5 mg, calcium stearate - 2 mg.

Pharmacological properties:

Derivative dihydropyridine – a blocker of slow calcium channels. Has anti-hypertensive and anti-anginal effect. Blocks calcium channels, reduces transmembrane transition of calcium ions to a cell (more in smooth muscle cells of vessels, than in cardiomyocytes).

Anti-hypertensive action is caused by direct vazodilatiruyushchy action on unstriated muscles of vessels. Has long dozozavisimy anti-hypertensive effect.

Amlodipin reduces myocardium ischemia (has anti-anginal effect) in two ways:

1) expands peripheral arterioles and thus reduces OPSS, reduces an afterload by heart, at this ChSS practically does not change that leads to decrease in consumption of energy and need of a myocardium for oxygen;

2) expands coronary and peripheral arteries and arterioles in not changed and in ischemic zones of a myocardium that increases intake of oxygen in a myocardium (especially at vasospastic stenocardia), reduces expressiveness of ischemia of a myocardium and prevents development of a spasm of coronary arteries (including caused by smoking).

At arterial hypertension the single dose provides clinically significant decrease in the ABP for 24 h (in position of the patient "lying" and "standing"). Thanks to the slow beginning of action амлодипин does not cause sharp decrease in the ABP. Does not reduce tolerance to an exercise stress and fraction of emission of a left ventricle.

At patients with stenocardia the single daily dose of an amlodipin increases time of performance of an exercise stress, slows down development of stenocardia and ischemic depression of a segment of ST (on 1 mm), reduces the frequency of attacks of stenocardia and consumption of nitroglycerine and other nitrates.

Reduces degree of a hypertrophy of a myocardium of a left ventricle, has anti-atherosclerotic and cardiotyre-tread effect at an ischemic heart disease.

At patients from the ischemic heart diseases (including coronary atherosclerosis with defeat of one vessel and to a stenosis of three and more arteries and atherosclerosis of carotid arteries) which transferred a myocardial infarction, transdermal transluminal angioplasty of coronary arteries (TLAP) or having stenocardia, use of an amlodipin prevents development of a thickening erotic-medii of carotid arteries, considerably reduces a lethality from the cardiovascular reasons, a myocardial infarction, stroke, TLAP, aortocoronary shunting, leads to decrease in number of hospitalization concerning unstable stenocardia and progressing of chronic heart failure, reduces the frequency of the interventions directed to recovery of a coronary blood-groove.

Amlodipin does not increase risk of death or development of the complications leading to deaths at patients with chronic heart failure (the III-IV functional class on classification of the New York Association of cardiologists (NYHA)) against the background of therapy by digoxin, diuretics and APF inhibitors.

Patients with chronic heart failure (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 exert impact on contractility and conductivity of a myocardium, does not cause reflex increase in ChSS, 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 concentration of lipids in a blood plasma and it can be applied at treatment of patients with bronchial asthma, a diabetes mellitus and gout.

Time of approach of effect of drug - 2-4 h, effect duration - 24 h. At long therapy the maximum decrease in the ABP occurs in 6-12 h after reception of an amlodipin inside. If after long treatment амлодипин to cancel, effective decrease in the ABP remains during 48 h after reception of the last dose. Then the ABP indicators gradually are returned to initial level within 5-6 days.

 

Pharmacokinetics. Absorption

Absorption is slow, does not depend on meal, makes about 90%. Bioavailability makes 60-90%, Cmax in blood serum is observed in 6-12 h after reception.

Distribution

Vd is equal to about 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 (95-97%) contacts proteins of a blood plasma. Amlodipin gets through GEB. At a hemodialysis is not removed. Css of an amlodipin in a blood plasma is reached in 7-8 days of constant administration of drug.

Metabolism

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.

Removal

After a single dose in T1/2 varies from 31 to 48 h, at repeated purpose of T1/2 makes about 45 h (that corresponds to purpose of drug of 1 times/). The general clearance of an amlodipin makes 0.116 ml / with/kg (7 ml/min., 0.42 l/h/kg).

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

Pharmacokinetics in special clinical cases

At elderly patients 65 years removal of an amlodipin are more senior it is slowed down (T1/2 increases to 65 h) in comparison with young people to patients. At elderly and young patients have a time necessary for achievement of Cmax of an amlodipin in a blood plasma, almost identical.

At patients with a liver failure and with heavy chronic heart failure of T1/2 increases to 56-60 h.

T1/2 from a blood plasma at patients with a renal failure increases to 60 h. Change of concentration of an amlodipin in a blood plasma does not correlate with degree of a renal failure.

Indications to use:

— arterial hypertension (monotherapy or in a combination with other antihypertensives);

— a stable angina of exertion, vasospastic stenocardia (Printsmetal's stenocardia) (monotherapy or in a combination with other anti-anginal means).

Route of administration and doses:

Pill is taken once inside, washing down with the necessary volume of water (up to 100 ml).

For treatment of arterial hypertension and stenocardia the initial dose makes 5 mg of 1 times/days. Depending on individual reaction of the patient if necessary the dose can be increased as much as possible to 10 mg of 1 times/days.

At arterial hypertension the maintenance dose can be 5 mg/days. At vasospastic stenocardia (Printsmetal's stenocardia) - 5-10 mg/days, the dose is accepted by 1 times/days.

Change of a dose at co-administration with thiazide diuretics, beta adrenoblockers and APF inhibitors is not required.

At patients with a liver failure, elderly patients change of a dose can be required, the initial dose at arterial hypertension can make 2.5 mg.

At purpose of drug patients with a renal failure do not need change of the mode of dosing.

Features of use:

At treatment of arterial hypertension of Amlorus® it is possible to apply in a combination with thiazide diuretics, alpha adrenoblockers, beta adrenoblockers and APF inhibitors.

For treatment of stenocardia of Amlorus® it is possible to combine with other anti-anginal means, for example, with nitrates of the prolonged or short action, beta adrenoblockers.

Амлорус® it can be applied and when the patient is predisposed to a vascular spasm (vasoconstriction).

Амлорус® does not influence plasma concentration of potassium ions, glucose, triglycerides, the general cholesterol, lipoproteids of low density, uric acid, creatinine and an urea nitrogen and it can be applied at treatment of patients with bronchial asthma, a diabetes mellitus and gout.

To patients with small body weight, to patients of low growth and patients with the expressed abnormal liver function as anti-hypertensive means of Amlorus® appoint in an initial dose 2.5 mg, as anti-anginal means - 5 mg.

During treatment it is necessary to control the body weight and consumption of sodium, purpose of the corresponding diet, observation at the stomatologist is shown (for prevention of morbidity, bleeding and a hyperplasia of gums).

Despite the absence of at withdrawal drug, before the termination of treatment gradual reduction of doses is recommended.

Influence on ability to driving of motor transport and to control of mechanisms

During treatment it is necessary to be careful at control of vehicles and occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

As the frequency of side reactions it is understood: very often (≥1/10); often (≥1/100, <1/10); infrequently (≥1/1000, <1/100); seldom (≥1/10 000, <1/1000); very seldom (<1/10 000), including separate messages.

From cardiovascular system: often - peripheral hypostases (anklebones and feet), a heart consciousness, feeling of heat and "inflows" of blood to face skin; infrequently - excessive decrease in the ABP, orthostatic hypotension, a vasculitis; seldom - development or aggravation of a course of chronic heart failure; very seldom - disturbances of a heart rhythm (including bradycardia, ventricular tachycardia and atrial fibrillation), a myocardial infarction, thorax pain.

From TsNS: often - increased fatigue, dizziness, a headache, drowsiness, migraine; infrequently - a febricula, a syncope, the increased sweating, an adynamy, hypesthesias, paresthesias, a peripheral neuropathy, a tremor, sleeplessness, lability of mood, unusual dreams, nervousness, a depression, alarm; seldom - spasms, apathy, agitation; very seldom - an ataxy, amnesia.

From sense bodys: infrequently - a ring in ears, vision disorders, eye pain, a diplopia, a xerophthalmia, conjunctivitis, accommodation disturbance, a food faddism; very seldom - a parosmiya.

From the alimentary system: often - an abdominal pain, nausea; infrequently - vomiting, 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 an urinary system: infrequently - the speeded-up urination, an urodynia, a nocturia, impotence; very seldom - a dysuria, a polyuria.

From respiratory system: infrequently - short wind, rhinitis, nasal bleeding; very seldom - cough.

From a musculoskeletal system: infrequently - an arthralgia, myotonia, a mialgiya, a dorsodynia, arthrosis; seldom - a myasthenia.

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

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

From a metabolism: very seldom - a hyperglycemia.

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

Others: infrequently - a gynecomastia, increase/decrease in body weight, a fever; very seldom - cold sweat.

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.

Amlodipin does not exert impact on pharmacokinetic parameters of digoxin and warfarin, does not influence the changes of a prothrombin time caused by warfarin.

Cimetidinum does not influence pharmacokinetics of an amlodipin.

Drugs of calcium can reduce effect of blockers of slow calcium channels (including an amlodipina).

Unlike other blockers of slow calcium channels of significant interaction at combined use with NPVP (including indometacin) it was revealed not.

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

Alfa1-adrenoblokatory, neuroleptics, Amiodaronum and quinidine can strengthen anti-hypertensive action of an amlodipin at combined use.

Blockers of slow calcium channels (including амлодипин) can increase expressiveness of negative inotropic effect of the antiarrhytmic drugs causing lengthening of an interval of QT (Amiodaronum, quinidine, procaineamide).

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

The single dose of a sildenafil in a dose of 100 mg 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.

Antiviral drugs (ритонавир) increase plasma concentration of blockers of slow calcium channels (including an amlodipina).

The single dose aluminum - and magniysoderzhashchy antacids has no significant effect on pharmacokinetics of an amlodipin.

Grapefruit juice can reduce concentration of an amlodipin in a blood plasma, however 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.

Contraindications:

— heavy arterial hypotension (systolic ABP less than 90 mm hg);

— cardiogenic shock;

— an acute myocardial infarction during the first 28 days;

— unstable stenocardia (except for vasospastic / Printsmetal's stenocardias);

— obstruction of the taking-out path of a left ventricle (including clinically significant stenosis of an aorta);

— age up to 18 years;

— lactose intolerance, deficit of lactase, glyukozo-galaktozny malabsorption;

— hypersensitivity to an amlodipin, other derivatives of dihydropyridine and other components of drug.

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 classification, arterial hypotension, an aortal stenosis, a mitral stenosis, a hypertrophic subaortic stenosis, advanced age.

 

Use of the drug AMLORUS® at pregnancy and feeding by a breast
Safety of use of an amlodipin at pregnancy is not established therefore use at pregnancy is possible only in that case when the advantage of use for mother exceeds potential risk for a fruit.

Are absent this, testimonial of excretion of an amlodipin with breast milk. However it is known that other blockers of slow calcium channels - dihydropyridine derivatives, are excreted with breast milk. In this connection, in need of purpose of the drug Amlorus® in the period of a lactation it is necessary to resolve an issue of the breastfeeding termination.

Women of childbearing age have to use reliable methods of contraception.

Use at abnormal liver functions
At patients with a liver failure change of a dose can be required, the initial dose at arterial hypertension can make 2.5 mg.

Use at renal failures
At purpose of drug patients with a renal failure do not need change of the mode of dosing.

Use for elderly patients
At elderly patients change of a dose can be required, the initial dose at arterial hypertension can make 2.5 mg.

Use for children
Drug is contraindicated to use at детй and teenagers to a vvozrasta up to 18 years (efficiency and safety are not established).

Overdose:

Symptoms: the expressed decrease in the ABP with possible development of reflex tachycardia and an excessive peripheral vazodilatation (there is a probability of emergence of the expressed and persistent arterial hypotension, including with development of shock and a lethal outcome).

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 the lower 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 - in/in administration of calcium of a gluconate. As амлодипин substantially contacts serum proteins, the hemodialysis is inefficient.

Storage conditions:

Drug should be stored in the unavailable to children, dry, protected from light place at a temperature not above 25 °C. A period of validity - 3 years.

Issue conditions:

According to the recipe

Packaging:

10 - planimetric strip packagings (3) - packs cardboard.