Amlodipin - Teva

General characteristics. Structure:

1 tablet contains: Active agent: Amlodipina безилат (амлодипин) - 6,944 mg (5,00 mg). Amlodipina безилат (амлодипин) - 13,888 mg (10,00 mg).

Excipients: Cellulose microcrystallic, calcium hydrophosphate (anhydrous), sodium carboxymethylstarch (type A), magnesium stearate.

Description

Tablets of 5 mg. Round biconvex tablets of white color. On one of the parties an engraving of "AB 5". Other party smooth.

Tablets of 10 mg. Round biconvex tablets of white color. On one of the parties dividing risk and an engraving of "AB 10". Other party smooth.

Pharmacological properties:

Pharmacodynamics. The blocker of "slow" calcium channels, derivative dihydropyridine - a blocker of "slow" calcium channels (BMKK) of the II generation, has anti-anginal and hypotensive effect. Blocks calcium channels, reduces transmembrane transition of calcium ions to 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 (GPVR), reduces an afterload by heart, reduces the need of a myocardium for oxygen. Expanding coronary arteries and arterioles in not changed and in ischemic zones of a myocardium, increases intake of oxygen in a myocardium (especially at vasospastic stenocardia); prevents a spasm of coronary arteries (including caused by smoking). At patients with stable stenocardia the single daily dose increases tolerance to an exercise stress, increases time before an attack of stenocardia and a "ischemic" depression of a segment of ST, reduces the frequency of attacks of stenocardia and consumption of nitroglycerine and other nitrates.

Renders long-term dozozavisimy hypotensive effect. Hypotensive action is caused by direct vazodilatiruyushchy 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"). Orthostatic hypotension at purpose of an amlodipin meets rather seldom. Does not cause decrease in fraction of emission of a left ventricle. Reduces degree of a hypertrophy of a myocardium of a left ventricle. 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, increases a glomerular filtration rate, possesses a weak natriuretic effect.

At a diabetic nephropathy does not increase expressiveness of a microalbuminuria. Does not exert any adverse impact on a metabolism and concentration of lipids of a blood plasma and it can be applied at therapy of patients with bronchial asthma, a diabetes mellitus and gout. Significant decrease in the ABP is observed in 6-10 hours, effect duration - 24 hours.

At 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 the carotid arteries which transferred a myocardial infarction, chrezkozhny transluminal angioplasty (TLAP) of coronary arteries or patients with stenocardia use of an amlodipin prevents development of a thickening erotic-medii of carotid arteries, reduces myocardial infarction, stroke mortality, TLAP, aortocoronary shunting; leads to decrease in frequency of development of 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 patients with HSN (the III-IV functional class on NYHA classification) against the background of therapy by digoxin, diuretics and inhibitors of an angiotensin-converting enzyme (APF). Patients with 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.

Pharmacokinetics. After intake амлодипин it is slowly absorbed from the digestive tract (DT). Average absolute bioavailability makes 64%, the maximum concentration (Cmax) in blood serum is observed in 6-9 hours. Equilibrium concentration (Css) are reached after 7-8 days of therapy.

Meal 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 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 active metabolism in a liver in the absence of significant effect of "the first passing". Metabolites have no essential pharmacological activity.

After a single dose the elimination half-life (T1/2) varies from 35 to 50 hours, at repeated use of T1/2 makes about 45 hours. About 60% of the dose accepted inside are removed by kidneys preferential in the form of metabolites, 10% - in not changed look, and 20-25% - through intestines with bile. The general clearance of an amlodipin makes 0,116 ml / with/kg (7 ml / ¼¿¡./kg, 0,42 l/h/kg).

At elderly patients (65 years are more senior) removal of an amlodipin is slowed down (T1/2 is equal to 65 h) in comparison with young patients, however this difference has no clinical value. Lengthening of T1/2 at patients with a liver failure assumes that at prolonged use cumulation of drug in an organism will be higher (T1/2 - to 60 h). The renal failure has no significant effect on kinetics of an amlodipin. At patients with a renal failure of change of concentration of an amlodipin in a blood plasma do not correlate with degree of a renal failure. Perhaps insignificant increase in T1/2. Amlodipin gets through a blood-brain barrier. At a hemodialysis is not removed.

Indications to use:

- arterial hypertension;
- stable angina of exertion and vasospastic stenocardia.

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. In the absence of therapeutic effect within 2-4 weeks the dose of drug can be increased to 10 mg/days once.

It is not required from elderly patients of Dose adjustment.
At patients with an abnormal liver function

In spite of the fact that T1/2 of an amlodipin, 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 - Teva in usual doses is recommended to apply (see the section "Special Instructions").

Features of use:

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

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

When using Amlodipin's - Teva at patients with chronic heart failure of III and IV functional classes on classification of NYHA edematization of lungs is possible.

At an acute myocardial infarction Amlodipin - Tev is appointed after stabilization of indicators of a hemodynamics (see the section "Contraindications").

Patients with a liver failure in need of Amlodipin's reception - Teva have to be under observation of the doctor.

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.

At patients with a renal failure control of a state is necessary. Efficiency and safety of use of drug of Amlodipin - Teva at hypertensive crisis is not established.

Despite the absence of at BMKK of a syndrome of "cancellation", drug Amlodipin - it is desirable to see off Tev the treatment termination, gradually reducing a drug dose.

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

Though against the background of Amlodipin's reception - Teva 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 - not less than 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; seldom - not less than 0,01%, but less than 0,1%; very seldom - less than 0,01%, including separate messages.

From the central nervous system: often - a headache (especially in an initiation of treatment), dizziness, increased fatigue, drowsiness; infrequently - a febricula, a hypesthesia, an adynamy, paresthesias, peripheral neuropathy, a tremor, sleeplessness, emotional lability, unusual dreams, nervousness. a hyperexcitability, a depression, alarm, the increased sweating; seldom - spasms, apathy, agitation; very seldom - an ataxy, amnesia, migraine.

From the alimentary system: often - nausea, abdominal pains; 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 - pancreatitis, gastritis, jaundice (usually cholestatic), a hyperbilirubinemia, increase in activity of "hepatic" transaminases, hepatitis.
From cardiovascular system: often - peripheral hypostases (anklebones and feet), heartbeat, "inflows" of blood to face skin; infrequently - excessive decrease in the ABP, orthostatic hypotension, a vasculitis; seldom - development or aggravation of a current of HSN; very seldom - a syncope, an asthma, disturbances of a heart rhythm (including bradycardia, ventricular tachycardia and atrial fibrillation), a myocardial infarction, thorax pain, a fluid lungs.

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

From an urinary system: infrequently - a pollakiuria, painful desires on an urination, a nocturia; very seldom - a dysuria, a polyuria.

From reproductive system and mammary glands: infrequently - a gynecomastia, impotence.
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: infrequently - an alopecia; seldom - dermatitis; very seldom - an alopecia, a xerodermia, a cold clammy sweat, disturbance of a xanthopathy.

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

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

Others: infrequently - decrease in body weight, increase in body weight, a food faddism, nasal bleeding, a fever.

Interaction with other medicines:

Amlodipin can safely be applied to therapy of arterial hypertension together with thiazide diuretics, alpha 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.

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

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

Erythromycin at combined use raises Cmax of an amlodipin at young patients for 22%, and at elderly - for 50%.

Beta adrenoblockers at simultaneous use with amlodipiny can cause an aggravation of a course of heart failure.

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 arterial hypertension 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.

Anti-retrovirus 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 or other components of drug;
• the expressed arterial hypotension (systolic the ABP less than 90 mm hg);
• cardiogenic shock;
• an acute myocardial infarction (during the first 28 days);
• unstable stenocardia (except for Printsmetal's stenocardia);
• obstruction of the taking-out path of a left ventricle;
• clinically significant stenosis of an aorta;
• age up to 18 years (efficiency and safety are not established).

With care: abnormal liver functions, a sick sinus syndrome (the expressed bradycardia, tachycardia), HSN of not ischemic etiology of the III-IV functional class on NYHA classification, arterial hypotension, an aortal stenosis, a mitral stenosis, an acute myocardial infarction (after the first 28 days), advanced age, a renal failure.

Use at pregnancy and in the period of a lactation

In pilot studies fetotoksichesky and embriotoksichesky effect of drug are not established, but use at pregnancy is possible only in that case when the advantage 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 BMKK - dihydropyridine derivatives, are excreted with breast milk. In this connection, in need of purpose of drug Amlodipin - Tev in the period of a lactation it is necessary to resolve an issue of the breastfeeding termination.

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, use 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 the volume of the circulating blood (VCB) 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 calcium of a gluconate. The hemodialysis is inefficient.

Storage conditions:

To store at a temperature not above 25 °C. To store in the place, unavailable to children! Period of validity of 5 years. Not to use after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Tablets of 5 mg and 10 mg.

On 10 tablets in the blister from Al/PVC/PVDC.

For a dosage of 5 mg: on 1 or 3 blisters in a pack cardboard together with the application instruction. For a dosage of 10 mg: on 1, 2 or 3 blisters in a pack cardboard together with the application instruction.