Amlodipin

General characteristics. Structure:

Active ingredient: amlodipine;

1 tablet contains an amlodipin of a besilat, in terms of амлодипин – 5 mg;

excipients: lactose, monohydrate; potato starch; povidone; calcium stearate.

Pharmacological properties:

Pharmacodynamics. Amlodipin – the selection blocker of "slow" calcium channels of group of derivatives of dihydropyridine of the second generation. Contacting dihydropyridinic receptors, blocks receipt of calcium ions in smooth muscle cells of vessels and a myocardium. Has the prolonged dozozavisimy anti-hypertensive effect. Hypotensive action is caused by the direct weakening impact on unstriated muscles of vessels, decrease in their general peripheric resistance of vessels (GPRV). Reduces expressiveness of ischemia of a myocardium due to expansion of peripheral arterioles and decrease in OPSS (after loading), ChSS at the same time changes a little. As a result of weakening of load of heart the need of a myocardium for oxygen decreases; expansion of large coronary arteries and arterioles both in not changed, and in ischemic zones of a cardiac muscle increases intake of oxygen in a myocardium. Poorly influences a sinus and atrioventricular node, slightly slows down AV-conductivity. Slows down aggregation of thrombocytes; increases a glomerular filtration rate, removal of sodium and a diuresis.

Thanks to gradual manifestation of action and the prolonged effect causes smooth decrease in the ABP (without acute hypotension) and the minimum reflex stimulation of a sympathetic nervous system. At an idiopathic hypertensia reduces degree of a hypertrophy of a myocardium of a left ventricle.

At patients with stenocardia Amlodipin increases time of performance of an exercise stress, development of an attack of stenocardia and depression of a segment of ST detains during loadings, reduces the frequency of attacks of stenocardia and quantity of the taken Tabulettaes Nitroglycerini.

With heart failure of the II-III functional class (on NYHA classification) амлодипин does not cause an aggravation of symptoms in patients.

At patients with heart failure (the III-IV class on NYHA) use of an amlodipin against the background of therapy by cardiac glycosides, β-adrenoblockers and APF inhibitors did not lead to increase in risk of a lethality.

Amlodipin does not exert any adverse impact on a metabolism, a lipidic range of a blood plasma and can be applied by patients with bronchial asthma, a diabetes mellitus and gout.

Pharmacokinetics. After intake in therapeutic doses Amlodipin is well soaked up, reaches the maximum concentration in blood in 6-12 h. Absolute bioavailability makes    64-80%. The use of food does not influence drug absorption. 90-97% of drug contact proteins of plasma. It Biotransformirutsya in a liver with formation of inactive metabolites. It is excreted with urine (60% in the form of metabolites, 10% – in not changed look), with bile (20-25% in the form of metabolites) and with breast milk.

Plasma elimination half-life makes 35-50 h in this connection Amlodipin it is possible to accept once a day. Equilibrium concentration in a blood plasma is reached in 7-8 days of regular use of drug.

The elimination half-life at an abnormal liver function and at elderly patients is extended. Changes of concentration of Amlodipin in plasma do not correlate with degree of a renal failure therefore Amlodipin can be applied in usual doses to treatment of such patients. Amlodipin does not leave during dialysis. 

Pharmaceutical characteristics.

Main physical and chemical properties. Tablets of white or almost white color with a flat surface, with risky and a facet.

Indications to use:

Arterial hypertension. Amlodipin is shown for treatment of arterial hypertension as means of the first row. Drug can be used for monotherapy of arterial hypertension at most of patients, in need of it it is possible to appoint also together with thiazide diuretics, a-adrenoblockers, β-adrenoblockers and APF inhibitors.

Coronary heart disease. Reduction of risk of need of carrying out revascularization of a myocardium and hospitalization because of stenocardia at patients on coronary heart disease.

Chronic stable stenocardia. As means of the first row for treatment of the ischemia of a myocardium caused as organic impassability (stable stenocardia), and a spasm or narrowing of coronary arteries (Printsmetal's stenocardia or alternative stenocardia).

Amlodipin it is possible to apply to reduction of risk of fatal forms of coronary heart disease, not fatal myocardial infarction and a stroke.

Drug can be used and when the clinical picture allows to allow only existence of a vasospasm or vasoconstriction though presence of the last is definitely not established.

Amlodipin it is possible to appoint as means of monotherapy or together with other anti-anginal drugs.

Route of administration and doses:

At arterial hypertension and chronic stable stenocardia adult appoint 5 mg of 1 times a day; in case of need, depending on individual reaction of the patient, a dose within 2 weeks increase to the maximum dose –10 mg of 1 times a day.

At coronary heart disease the recommended dose makes 5-10 mg of 1 times a day.

At a combination therapy the dose of an amlodipin does not need to be changed.

It is recommended to adhere to the same time of administration of drug.

Features of use:

At the beginning of therapy the exacerbation of stenocardia is possible.

Restrictions at use: heart failure of the IV functional class (on NYHA classification), heavy abnormal liver functions, systolic pressure is less than 100 mm Hg, ChSS is less than 55 beats/min. At an aortal and mitral stenosis, a subaortic stenosis care is necessary because because of the hypotension caused by drug providing vitals with oxygen can decrease.

At Amlodipin's use for treatment of patients with heart failure of the III-IV functional class (on NYHA classification) increase in number случав a fluid lungs is noted. At patients with severe forms of heart failure Amlodipin is appointed with care, especially in a combination with β-blockers..........

The recommended daily dose for patients with a liver failure should not exceed 5 mg. It is necessary to control the level of liver enzymes constantly.

At identical doses patients of both elderly, and younger age equally well transfer Amlodipin. For patients of advanced age the daily dose should not exceed 5 mg.

The patient with a renal failure Amlodipin appoint in usual doses.

Amlodipin is not brought during a hemodialysis therefore dose adjustment for patients who are on a hemodialysis is not obligatory. At patients with arterial hypertension and a hypovolemia which are on a hemodialysis connected with Amlodipin's reception vasodilation, can cause a considerable lowering of arterial pressure.

At Amlodipin's use for patients with a diabetes mellitus it is necessary to consider a possibility of development of a hyperglycemia.

Ability to influence speed of response at control of motor transport or work with other mechanisms. Amlodipin does not influence ability to drive the car and other mechanisms, however because of possibility of differences of arterial pressure or development of side reactions from a nervous system it is necessary to be careful at activity which demands the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Co of the party of cardiovascular system: often – peripheral hypostases (anklebones and feet), the accelerated heartbeat; sometimes – arterial hypotension, a vasculitis; very seldom – disturbances of a heart rhythm (including bradycardia, ventricular tachycardia and atrial fibrillation), a myocardial infarction, a syncope;

from a nervous system and bodies чувств:часто – feeling of heat and "inflows" of blood, increased fatigue, dizziness, a headache, drowsiness; sometimes – an indisposition, the increased sweating, an adynamy, hypesthesias, paresthesias, a peripheral neuropathy, a tremor, sleeplessness, change of mood, a vision disorder, a ring in ears, change of flavoring feelings;

from urinogenital system: sometimes – increase in frequency and frustration of an urination, a nocturia, impotence, a gynecomastia;

from a digestive tract: often – an abdominal pain, nausea; sometimes – vomiting, a lock, dyspepsia, diarrhea, dryness in a mouth, intestinal dysfunction; seldom – a hyperplasia of gums; very seldom – gastritis, pancreatitis, a hyperbilirubinemia, jaundice (usually cholestatic), increase in activity of hepatic transaminases, hepatitis;

from a musculoskeletal system: sometimes – an arthralgia, myotonia, a hyper tone of muscles, a mialgiya, a dorsodynia;

from system кроветворения:очень it is rare – a Werlhof's disease, a leukopenia, thrombocytopenia;

from a metabolism: very seldom – a hyperglycemia;

from respiratory system: sometimes – short wind, rhinitis; very seldom – cough;

allergic reactions: sometimes – an itch, rash, an alopecia; very seldom – a Quincke's disease, a multiformny erythema, exfoliative dermatitis;

others: sometimes –увеличение / decrease in body weight; very seldom – disturbance of a xanthopathy.

Interaction with other medicines:

Amlodipin it is possible to apply along with thiazide diuretics, α-adrenoblockers,    β-adrenoblockers, APF inhibitors, nitrates of the prolonged action, nitroglycerine which is applied sublingual, with non-steroidal anti-inflammatory drugs, antibiotics and peroral hypoglycemic drugs.

Simultaneous use of Amlodipin and digoxin does not change digoxin level in blood serum and its renal clearance; joint reception of Cimetidinum does not change Amlodipin's pharmacokinetics.

Amlodipin of in vitro does not influence linkng with blood proteins of digoxin, warfarin and indometacin. Simultaneous use of Amlodipin does not change influence of warfarin on a prothrombin time.

Amlodipin significantly does not influence cyclosporine pharmacokinetics.

Means for an inhalation anesthesia, Amiodaronum, quinidine, other antagonists of calcium can strengthen Amlodipin's action. It is necessary to avoid a combination with Amiodaronum at patients with an atrioventricular block and a sick sinus syndrome. At simultaneous use of means for the general anesthesia strengthening of anti-hypertensive action of Amlodipin is possible.

Blockers of β-adrenoceptors exponentiate anti-anginal and hypotensive actions of Amlodipin, at the same time oppressing reflex tachycardia. Nitrates exponentiate anti-anginal action of Amlodipin, however the therapeutic value of a combination considerably decreases because of reflex tachycardia and a possibility of development of arterial hypotension.

At simultaneous reception with MAO inhibitors observes strong hypotensive effect, with barbiturates, carbamazepine, Phenytoinum, a pyrimidine decrease in efficiency of Amlodipin is possible.

Tricyclic antidepressants and alcohol can increase anti-hypertensive action of Amlodipin.

Contraindications:

Hypersensitivity to an amlodipin, other components of drug, dihydropyridines; unstable stenocardia (except for Printsmetal's stenocardia), cardiogenic shock, clinically significant aortal stenosis, pregnancy and the period of feeding by a breast.

Use during pregnancy or feeding by a breast. Safety of use of Amlodipin during pregnancy and feeding by a breast is not established. Therefore Amlodipin's use during pregnancy is possible only in cases if there is no safer alternative, and the risk connected with a disease exceeds potential harm of treatment for mother and a fruit. For the period of treatment by Amlodipin feeding by a breast should be stopped.

Children. Experience of use of Amlodipin for treatment of children is absent therefore drug is not used in pediatric practice. 

Overdose:

Symptoms: excessive peripheral vasodilation with the expressed and long lowering of arterial pressure, tachycardia, symptoms of deterioration in perfusion of vitals.

Treatment: in certain cases there can be useful a gastric lavage, purpose of enterosorbents, giving to the patient of horizontal position of a body with the raised legs, monitoring of function of cardiovascular and respiratory systems, control of the general blood circulation and a diuresis; symptomatic and maintenance therapy, intravenous administration of liquid, gluconate of calcium, dopamine, phenylephine hydrochloride. The hemodialysis is inefficient.

Storage conditions:

Period of validity 2 years. To store in original packaging, at a temperature not over 25 ºС. To store in unavailable for a deteymesta.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in the blister, 3 blisters to a vpachka.