Amlodipin-FT

General characteristics. Structure:

Active ingredient: 5 and 10 mg of an amlodipin (in the form of an amlodipin of a besilat respectively on 6,934 mg and 13,868 mg).

Excipients: sodium krakhmalglikolit (type A), calcium hydrophosphate anhydrous, magnesium stearate, silicon dioxide kolloydny anhydrous, cellulose microcrystallic.

Hypotensive and antiarrhythmic medicine.

Pharmacological properties:

Pharmacodynamics. Amlodipin – a blocker of slow calcium channels or the antagonist of calcium ions, blocks receipt of calcium ions through membranes in smooth muscle cells of a myocardium of vessels.

The mechanism of hypotensive action of an amlodipin is caused by the direct weakening impact on smooth muscle cells of vessels.

The exact mechanism of action of an amlodipin at stenocardia is not finalized, but амлодипин reduces ischemia the next two ways:
1. Amlodipin expands peripheral arterioles and, thus, reduces the general peripheric resistance (afterload) for which overcoming cardiac performance is spent. As heart rate does not change, reduction of load of heart leads to decrease in consumption of energy and oxygen requirement.
2. The mechanism of action of an amlodipin possibly also includes expansion of the main coronary arteries and coronary arterioles both in invariable, and in ischemic zones of a myocardium. This dilatation increases intake of oxygen in a myocardium at больныз vazopastichesky stenocardia (Printsmetal's stenocardia or alternative stenocardia) and prevents development of the coronary vasoconstriction caused by smoking.

At patients with arterial hypertension the single daily dose of an amlodipin provides clinically significant lowering of arterial pressure for 24 hours 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 the single daily dose of an amlodipin increases time of performance of an exercise stress, development of an attack of stenocardia and depression of a segment of ST detains (on 1 mm) during its performance, reduces the frequency of attacks of stenocardia and consumption of Tabulettaes Nitroglycerini.

Pharmacokinetics. Absorption. After intake in therapeutic doses амлодипин it is well soaked up, reaching the maximum concentration in blood in 6-12 hours after reception. Absolute bioavailability by calculations makes 64-80%. The volume of distribution is equal to about 21 l/kg. Meal does not influence absorption of an amlodipin.

The researches in vitro showed that about 97,5% of the circulating amlodipin are connected with proteins of plasma.

Biotransformation/removal. Plasma elimination half-life makes about 35-50 hours that corresponds to purpose of drug of 1 times a day. Stable equilibrium concentration in plasma is reached in 7-8 days of constant administration of drug. Amlodipin biotransformirutsya in a liver with formation of inactive metabolites; 10% of invariable drug and 60% of metabolites are removed with urine.

Use for elderly people. At elderly and more young people, necessary for achievement of the maximum concentration of an amlodipin in a blood plasma, almost identical. At people of advanced age the tendency to decrease in clearance of an amlodipin is noted that leads to increase in UAC (the area of a zone under a curve concentration time) and an elimination half-life. As well as it was supposed, at patients, various age groups having congestive heart failure increase in AUC and an elimination half-life of drug was observed.

Indications to use:

· arterial hypertension;
· stable stenocardia and vasospastic stenocardia (Printsmetal's stenocardia).

Route of administration and doses:

The usual initial dose at arterial hypertension and stenocardia makes 5 mg/days preferably at the same time day. Depending on the clinical answer, increase in a dose to 10 mg/days is possible. At simultaneous use of thiazide diuretics of β-blockers and inhibitors of an angiotensin-converting enzyme of a korrektsiidoza it is not required. To elderly persons, persons with small body weight, and to patients with an abnormal liver function it is possible to appoint a dose of 2,5 mg. It is possible to appoint the same dose at a combination of an amlodipin with other anti-hypertensive means. The dose of drug should be chosen taking into account individual needs of the patient. Usually selection of a dose (titration) is carried out from 7 to 14 days that gives the chance to the doctor to estimate the answer of the patient to each dose. At clinical need the titration can be accelerated if there is an opportunity often to estimate the patient's condition.

At stable vasospastic stenocardia the recommended dose makes 5-10 mg, the low dose is recommended elderly and sick with abnormal liver functions. The dose of 10 mg is necessary for most of patients for obtaining adequate effect. The recommended dose interval for patients with diseases of coronary arteries makes 5-10 mg a day. In clinical trials the dose of 10 mg a day was required for most of patients.

Use for children. Safety and efficiency of an amlodipin at use for children is not established.

Use for patients with the broken function of a liver. See the section "Precautionary measures".

Features of use:

Safety and efficiency of use of an amlodipin at hypertensive crisis were not estimated.

Patients with heart failure. This category of patients амлодипин should apply with care. In long-term placebo - a controlled research at patients with heart failure of heavy degree (a class III and IV on NYHA classification) at use of an amlodipin the frequency of cases of edematization of lungs was higher in comparison with placebo use, but this effect was not connected with emergence of an exacerbation of heart failure.

Patients with an abnormal liver function. The elimination half-life of an amlodipin increases at patients with an abnormal liver function, however recommendations about a dosage of drug are not developed yet. Therefore this category of patients should use drug with care.

Patients of advanced age. It is necessary to increase a dose of drug of this category of patients with care.

Patients with a renal failure. This category of patients should apply usual doses of drug. Changes of concentration of an amlodipin in a blood plasma do not correlate with degree of renal failures. Amlodipin does not leave by dialysis.

Amlodipin does not influence results of laboratory researches.

It is not recommended to apply амлодипин together with grapefruit or grapefruit juice as at some patients bioavailability can be increased that will lead to strengthening of hypotensive effect of drug.

Low growth and the patient with the expressed abnormal liver functions the smaller dosage of an amlodipin can be required by patients with small body weight.

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

The dosing mode for elderly patients same, as well as for patients of other age groups. At increase in a dose careful observation of elderly patients is necessary.

Despite the absence of at blockers of "slow" calcium channels of a syndrome of "cancellation", before the termination of treatment gradual reduction of doses is recommended.

Amlodipin does not influence plasma concentration of K+, glucose, triglycerides, the general cholesterol, LPNP, uric acid, creatinine and nitrogen of uric acid therefore Amlodipin-FT can be applied with care at patients with bronchial asthma, a diabetes mellitus and gout.

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

It is necessary to make the decision on the termination of reception by nursing mothers of drug or on the breastfeeding termination, proceeding from importance of administration of drug for mother or advantages of breastfeeding.

Amlodipin exerts impact on ability to drive the car and to use the equipment when at the patient dizziness, a headache, weakness or nausea develops. These effects can influence the speed of reaction of the patient. In similar situations care, especially in an initiation of treatment is necessary.

Side effects:

Side reactions about which it was reported at use of an amlodipin are given below by systems and classes of bodies and emergence frequency: very often (≥ 1/10), it is frequent (≥ 1/100 - <1/10), infrequently (≥ 1/1000 - ≤ 1/100), is rare (≥ 1/10000 - ≤ 1/1000), is very rare (≤ 1/10000).

From blood and lymphatic system. Very seldom: leukopenia, thrombocytopenia.

From immune system. Very seldom: allergic reactions.
Disturbances of metabolism and alimentary frustration. Very seldom: hyperglycemia.

Mental disturbances. Infrequently: sleeplessness, changes of mood (including uneasiness), a depression. Seldom: confusion of consciousness.

From a nervous system. Often: drowsiness, dizziness, a headache (mainly in an initiation of treatment). Infrequently: tremor, dysgeusia, hypesthesia, paresthesia. Very seldom: hyper tone, peripheral neuropathy.

From organs of sight. Infrequently: a vision disorder (including a diplopia).

From acoustic organs and balance. Infrequently: a ring in ears.

From heart. Infrequently: the strengthened heartbeat.

Very seldom: a myocardial infarction, arrhythmia (including bradycardia, ventricular tachycardia and atrial fibrillation).

From vessels. Often: inflows. Infrequently: arterial hypotension. Very seldom: vasculitis.

Respiratory, thoracic and mediastinal disturbances. Infrequently: диспноэ, rhinitis. Very seldom: cough.

From digestive tract. Often: abdominal pain, nausea. Infrequently: vomiting, dyspepsia, disturbances of a vermicular movement of intestines (including a lock and diarrhea), dryness in a mouth.

Very seldom: pancreatitis, gastritis, hyperplasia of gums.

From gepatobiliarny system. Very seldom: hepatitises, jaundice, increase in level of liver enzymes (that was associated with a cholestasia more often).

From skin and hypodermic fabric. Infrequently: alopecia, purpura, change of coloring of skin, perspiration, itch, rash, dieback. Very seldom: Quincke's disease, multiformny erythema, small tortoiseshell, exfoliative dermatitis, Stephens Johnson's syndrome, Quincke's edema, photosensitization.

From musculoskeletal and connecting fabrics. Often: hypostasis of shins. Infrequently: arthralgia, mialgiya, spasms, dorsodynia.

From kidneys and urinary tract. Infrequently: disturbance of an urination, a nocturia, the increased urination frequency.

From reproductive system and mammary glands. Infrequently: impotence, gynecomastia.

The general disturbances and states in an injection site. Often: hypostasis, fatigue. Infrequently: pain behind a breast, an adynamy, pain, an indisposition.

Researches. Infrequently: increase or degrowth of a body.

In case of others, not mentioned above, side effects or deterioration in your health it is necessary to consult with the doctor

Interaction with other medicines:

Amlodipin safely applied together with thiazide diuretics, alpha adrenoblockers, beta adrenoblockers, inhibitors of an angiotensin-converting enzyme, nitrates of long action, the nitroglycerine applied sublingual, non-steroidal anti-inflammatory drugs, antibiotics and peroral hypoglycemic drugs.

Results of the researches in vitro with use of plasma of the person demonstrate to what амлодипин does not influence linkng with proteins of drugs, a podvergnutykhtestirovaniya (digoxin, Phenytoinum, warfarin and indometacin).

SIMVASTATIN: Simultaneous repeated use of an amlodipin in a dose of 10 mg with simvastatiny in a dose of 80 mg led to increase in influence of a simvastatin by 77% in comparison with monotherapy simvastatiny. It is recommended to limit a dose of a simvastatin at the patients accepting амлодипин to 20 mg a day.

GRAPEFRUIT JUICE: a concomitant single dose of 240 ml of grapefruit juice and 10 mg of an amlodipin inside at 20 healthy volunteers had no significant effect on pharmacokinetics of an amlodipin. In this research it was not represented possible to study influence of genetic polymorphism of CYP3A4 (the main enzyme which is responsible for metabolism of an amlodipin). Reception of an amlodipin with grapefruit or grapefruit juice is not recommended as bioavailability and respectively hypotensive action of an amlodipin can increase.

CYP3A4 INHIBITORS: The concomitant use of diltiazem in a dose of 180 mg and an amlodipina in a dose of 5 mg at patients of advanced age (69-87 years) led to increase in system influence of an amlodipin by 57%. The concomitant use with erythromycin at healthy volunteers (aged from 18 up to 43 years) did not lead to significant change of system influence of an amlodipin (22% increase in AUC). In spite of the fact that the clinical importance of these data is not clear, at elderly people pharmacokinetic changes can be accurately expressed.

Strong CYP3A4 inhibitors (for example, кетоконазол, итраконазол, ритонавир) can increase concentration of an amlodipin more than diltiazem. It is necessary to apply with care амлодипин in a combination with CYP3A4 inhibitors.

CYP3A4 STIMULATORS: There are no CYP3A4 stimulators given on influence on амлодипин. The concomitant use of stimulators of CYP3A4 (for example, the rifampicin, a St. John's Wort which is made a hole) can lead to decrease in concentration of an amlodipin in a blood plasma. It is necessary to apply with care амлодипин in a combination with CYP3A4 stimulators. In the researches of significant changes of pharmacokinetics both an amlodipin given below, and other medicines at a concomitant use were not noted.

Special researches: influence of other medicines on амлодипин. CIMETIDINUM: the concomitant use of an amlodipin and Cimetidinum was not followed by change of pharmacokinetics of an amlodipin.

ALUMINIUM/MAGNESIUM (antacid): the single dose aluminum/magnesium of the containing antacids with amlodipiny had no significant effect on pharmacokinetics of an amlodipin.

SILDENAFIL: the single dose of a sildenafil in a dose of 100 mg at patients with an essential hypertension did not exert impact on parameters of pharmacokinetics of an amlodipin. At the combined use of an amlodipin and sildenafil both drugs had independent hypotensive effect.

DANTROLEN (infusion): at use of verapamil and a dantrolen intravenously at animals the fibrillation of ventricles and cardiovascular insufficiency with a lethal outcome which were followed by a hyperpotassemia developed. Due to the risk of emergence of a hyperpotassemia it is recommended to avoid co-administration of blockers of calcium channels, such as амлодипин, to patients with risk of development of a malignant hyperthermia or for treatment of a malignant hyperthermia.

Special researches: influence of an amlodipin on other medicines. ATORVASTATIN: repeated use of an amlodipin in a dose of 10 mg and an atorvastatina in a dose of 80 mg was not followed by considerable changes of equilibrium indicators of pharmacokinetics of an atorvastatin.

DIGOXIN: at simultaneous use of an amlodipin with digoxin at healthy volunteers serumal levels and renal clearance of digoxin did not change.

ETHANOL (alcohol): at single and repeated use in a dose of 10 mg амлодипин had no significant effect on ethanol pharmacokinetics.

WARFARIN: амлодипин did not influence the changes of a prothrombin time caused by warfarin.

CYCLOSPORINE: pharmacokinetic researches showed what амлодипин does not cause considerable changes of pharmacokinetics of cyclosporine.

LITHIUM: at combined use with drugs of lithium strengthening of manifestations of their neurotoxicity is possible.

Contraindications:

· the known hypersensitivity to an amlodipin, digdropiridina and/or to other components of drug;
· unstable stenocardia;
· clinically significant aortal stenosis;
· arterial hypotension (ABP less than 90 mm of mercury.)
· acute myocardial infarction;
· shock (including cardiogenic shock);
· children's age up to 18 years (there is no experience of a clinical use);
· pregnancy and the period of a lactation (see the section Use at pregnancy and during feeding by a breast).

With care appoint to patients: with abnormal liver functions, a sick sinus syndrome (the expressed bradycardia, tachycardia), chronic heart failure of the III-IV class in a decompensation stage, soft or moderate degree of arterial hypotension, an aortal and/or mitral stenosis, a hypertrophic subaortic stenosis, an acute myocardial infarction (and within 1 month after), a diabetes mellitus, disturbances of a lipidic profile, advanced age.

Because efficiency and safety of an amlodipin at children up to 18 years are definitely not established, it is necessary to refrain from its appointment to patients of this age category.

Overdose:

Symptoms: the expressed decrease in the ABP with possible development of reflex tachycardia, 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).

Lecheniye:naznacheniye of absorbent carbon (especially in the first 2 hours after overdose) a gastric lavage (in some cases), giving of sublime situation to extremities, active maintenance of function of cardiovascular system, control of indicators of function of heart and lungs, control of volume of the circulating blood and a diuresis. For recovery of a tone of vessels and the ABP if there are no contraindications, there can be useful a use of vasoconstrictive drugs; for elimination of effects of blockade of calcium channels - intravenous administration of a gluconate of calcium. In view of the fact that амлодипин substantially contacts proteins of plasma, the hemodialysis is not effective.

Storage conditions:

To store in the place protected from moisture at a temperature not over +25 ºС. To store in the place, unavailable to children. Period of validity 2 years.

Issue conditions:

According to the recipe

Packaging:

Tablets in a blister strip packaging No. 10х1, No. 10х2, No. 10х3 and in banks No. 50. Together with a leaf insert 1, 2 either 3 blister strip packagings or bank are located in a pack from a cardboard.