Aladin

General characteristics. Structure:

Active ingredient: 1 tablet contains an amlodipin of a besilat of 13,90 mg or 6,95 mg (in terms of амлодипин 10 mg or 5 mg);

excipients: tablets Aladin of 10 mg – lactoses monohydrate, potato starch, кросповидон, коповідон, silicon dioxide colloid anhydrous, magnesium stearate;

the mg tablets Аладин® 5 – lactoses monohydrate, starch corn, sodium of a kroskarmeloz, povidone, silicon dioxide colloid anhydrous, magnesium stearate.

Pharmacological properties:

Pharmacodynamics. Amlodipin is the antagonist of calcium (derivative dihydropyridine) which blocks receipt of calcium ions in a myocardium and in cells of unstriated muscles.

The mechanism of hypotensive action of an amlodipin is caused by directly weakening action on unstriated muscles of vessels. The exact mechanism of anti-anginal effect of an amlodipin is studied insufficiently, however stated below effects play a part.

Amlodipin expands peripheral arterioles and thus reduces the peripheric resistance (afterload). As the cordial rhythm remains stable, decrease in load of heart leads to decrease in consumption of energy and need of a myocardium for oxygen.

Expansion of the main coronary arteries and coronary arterioles (normal and ischemic), perhaps, also plays a role in the mechanism of action of an amlodipin. Such expansion raises a myocardium saturation oxygen at patients with a spasm of a coronary artery (stenocardia of Printsmetall or alternative stenocardia).

At patients with arterial hypertension use of drug of 1 times a day provides clinically significant lowering of arterial pressure within 24 hours in situation both lying, and standing. Due to the slow beginning of action of an amlodipin acute arterial hypotension usually is not observed.

At patients with stenocardia at use of one daily dose of drug the general time of an exercise stress, time prior to the beginning of stenocardia and time to 1 mm of a depression of a segment of ST raises. Drug reduces the frequency of attacks of stenocardia and reduces the need for nitroglycerine use.

Amlodipin is not associated with any side metabolic effects or changes of level of lipids in a blood plasma and can be applied to patients with asthma, a diabetes mellitus and gout.

Pharmacokinetics. Absorption/distribution. After oral administration of therapeutic doses амлодипин it is gradually absorbed in a blood plasma. Absolute bioavailability of not changed molecule makes about 64-80%. The maximum concentration in a blood plasma is reached within 6-12 hours after use. The volume of distribution makes about 21 l/kg; the dissociation constant of acid (rka) of an amlodipin makes 8,6. Linkng of an amlodipin with proteins of a blood plasma makes about 97,5%.

The simultaneous use of food does not influence absorption of an amlodipin.

Metabolism/removal. Plasma elimination half-life of blood makes about 35-50 hours. Equilibrium concentration in a blood plasma is reached after 7-8 days of continuous use of drug. Amlodipin is mainly metabolized with formation of inactive metabolites. About 60% of the entered dose are removed with urine of which about 10% make амлодипин in not changed look.

Patsiyentypozhily age. Time of achievement of equilibrium concentration of an amlodipin in plasma is similar at patients of advanced age and at adult patients. The clearance of an amlodipin is usually a little reduced that at patients of advanced age "concentration/time" (AUC) and a drug elimination half-life leads to increase in the area under a curve.

Patsiyentysnarusheny of functions of kidneys. Amlodipin biotransformirutsya extensively to inactive metabolites. 10% of an amlodipin are allocated in not changed view with urine. Changes of concentration of an amlodipin in a blood plasma do not correlate with extent of disturbance of functions of kidneys. Patients with disturbance of functions of kidneys can apply usual doses of an amlodipin. Amlodipin does not leave by dialysis.

Patsiyentysnarusheny of function of a liver. Information on use of an amlodipin to patients with an abnormal liver function is very limited. At patients with a liver failure the clearance of an amlodipin is reduced that leads to increase in duration of half-life and to increase in AUC approximately by 40-60%.

Children. Usually the clearance at oral administration to children from 6 to 12 years and from 13 to 17 years made 22,5 and 27,4 l/hour respectively for boys and 16,4 and 21,3 l/hour respectively for girls. Considerable variability of exposure at different patients is observed. Information concerning patients is younger than 6 years is limited.

Pharmaceutical characteristics

Main physical and chemical properties: Aladin of 10 mg – tablets of white or almost white color with a flat poyoverkhnost, with risky and a facet; Aladin of 5 mg – tablets of a round form with a biconvex surface of white or almost white color. On a surface of tablets the mramornost is allowed.

Period of validity. Aladin of 10 mg – 3 years. Aladin of 5 mg – 2 years.

Not to use drug after the termination of the period of validity specified on packaging.

Indications to use:

– Arterial hypertension.

– Chronic stable stenocardia.

– Vasospastic stenocardia (Printsmetall stenocardia).

Route of administration and doses:

Adults. For treatment of arterial hypertension and stenocardia a usual initial dose of drug Aladin makes 5 mg of an amlodipin of 1 times a day. Depending on reaction of the patient to therapy the dose can be raised to the maximum dose that makes 10 mg of 1 times a day.

Patients with stenocardia can use drug as monotherapy or in a combination with other anti-anginal medicines at resistance to nitrates and/or adequate doses of beta-blockers.

There is an experience of use of drug in a combination with thiazide diuretics, alpha blockers, beta-blockers or inhibitors of an angiotensin-converting enzyme to patients with arterial hypertension.

There is no need for selection of a dose of drug at simultaneous use with thiazide diuretics, beta-blockers and inhibitors of an angiotensin-converting enzyme.

Children since 6 years with arterial hypertension. The recommended initial dose of drug Aladin for this category of patients makes 2,5 mg of 1 times a day. If the necessary level of arterial pressure is not reached within 4 weeks, it is possible to increase a dose to 5 mg a day. Use of drug in doses higher than 5 mg for this category of patients was not investigated.

Patsiyentypozhily age. There is no need for selection of a dose for this category of patients. Increase in a dose needs to be carried out with care.

Patsiyentysnarusheny функциипочек.

It is recommended to apply usual doses of drug as changes of concentration of an amlodipin in a blood plasma are not connected with severity of a renal failure. Amlodipin is not brought by dialysis.

Patients with a liver failure.

Drug doses for use from easy to moderate severity are not established to patients with a liver failure therefore selection of a dose should be carried out with care and to begin use with the smallest dose (see the section "Features of Use" and "Pharmacological properties. Pharmacokinetics").

Features of use:

Use during pregnancy of an ilikormleniye a breast

Safety of use of an amlodipin is not established to women during pregnancy.

It is recommended to apply амлодипин during pregnancy only in cases, when there is no safer alternative, and the risk connected with a disease exceeds possible harm from treatment for mother and a fruit.

It is unknown whether gets амлодипин into breast milk. At making decision on feeding continuation by a breast or about use of an amlodipin it is necessary to estimate advantage of feeding by a breast for the child and advantage of use of drug for mother.

Fertility. It was reported about reversible biochemical changes of a head of a spermatozoon at some patients at use of blockers of calcium channels. Clinical information on potential influence of an amlodipin on fertility is not enough.
Children

To use drug to children from 6 years. Influence of an amlodipin on the arterial pressure of patients up to 6 years is unknown.

It is necessary to begin use of drug with the smallest dose. It is necessary to be careful both at the beginning of drug use, and during increase in a dose. Slow selection of a dose and careful observation of a condition of the patient can be necessary for patients with a heavy liver failure.

Throughout the entire period of treatment it is necessary to control the body weight and the use of sodium, purpose of the corresponding diet, and also daily control of arterial pressure.

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

Use by the patient with heart failure. This category of patients Aladin should apply with care.

Use by a bolnymsnarusheniye of function of a liver. The elimination half-life of Aladin, as well as other antagonists of calcium, increases at patients with an abnormal liver function. For this reason to use drug it is necessary for such patients with extra care and only under careful observation of the doctor.

Primeneniyebolnympozhily age. It is necessary to raise a dose of drug of this category of patients with care.

Primeneniyebolnymspochechny insufficiency. Aladin to apply to this category of patients in usual doses. Change of concentration of an amlodipin in a blood plasma does not correlate with severity of a renal failure. Amlodipin is not brought by dialysis. Amlodipin does not influence results of laboratory researches.

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

Alcohol intake during use of drug is contraindicated.
Ability to influence speed of response at control of motor transport or work with other mechanisms

Aladin can slightly or moderately influence ability to manage motor transport or to work with other mechanisms. It is necessary to be careful, especially at the beginning of therapy.

Speed of response can be reduced in the presence of such symptoms as dizziness, a headache, confusion of consciousness or nausea.

Side effects:

From blood and lymphatic system. Thrombocytopenia, leykotsitopeniya.

From immune system. Allergic reactions.

Disturbances of metabolism and alimentary frustration. Hyperglycemia.

From mentality. Sleeplessness, change of mood (including uneasiness), a depression, confusion of consciousness.

From a nervous system. Drowsiness, dizziness, a headache (mainly in an initiation of treatment), fatigue, an adynamy, spasms, the increased perspiration, a tremor, a dysgeusia, синкопэ, a hypesthesia, paresthesia, a hyper tone, peripheral neuropathy.

 From organs of sight. A vision disorder (including a diplopia), dacryagogue.

 From acoustic organs and a labyrinth. A ring in ears.

From heart. The strengthened heartbeat, an asthma, a stethalgia. As well as during reception of other antagonists of calcium, the single undesirable phenomena which cannot be separated from effects of the natural course of a basic disease were described: a myocardial infarction, arrhythmia (including bradycardia, ventricular tachycardia and atrial fibrillation), and also a retrosternal pain.

From vessels. Face reddening, inflows, arterial hypotension, vasculitis, peripheral hypostases.

Respiratory, thoracic and mediastinal disturbances. Диспноэ, rhinitis, cough.

From digestive tract. Nausea, vomiting, an abdominal pain, dyspepsia, discomfort in epigastric area, dryness in a mouth, disturbance of a vermicular movement of intestines (including a lock, diarrhea and a meteorism), pancreatitis, gastritis, a hyperplasia of gums.

From gepatobiliarny system. Hepatitises, jaundice, increase in level of liver enzymes (that most often was associated with a cholestasia).

From skin and hypodermic fabrics. A Quincke's disease (Quincke's edema), rash, an itch, a multiformny erythema, a small tortoiseshell, an alopecia, a purpura, skin discoloration, feeling of heat, the increased sweating, photosensitivity, exfoliative dermatitis, Stephens-Johnson's syndrome.

From skeletal and muscular and connecting fabrics. Puffiness of shins, arthralgia, mialgiya, myotonia, dorsodynia.

From kidneys and urinary path. Insignificant increase in a daily urine, nocturia, urination disturbance, increase in frequency of an urination.

From reproductive system and mammary glands. Gynecomastia, sexual dysfunction.

The general disturbances and states in an injection site. Hypostasis, fatigue, pain, indisposition, increase or degrowth of a body.

After drug withdrawal side effects usually completely disappear.

It was reported about exceptional cases of development of an extrapyramidal syndrome.

Interaction with other medicines:

Influence of other medicines on амлодипин.

CYP3A4 inhibitors. At simultaneous use of an amlodipin and CYP3A4 inhibitors, such as erythromycin to younger patients or diltiazem to the senior patients, concentration of an amlodipin in a blood plasma increased by 22% and 50% respectively. Clinical value of these data is unknown. It is impossible to exclude that powerful CYP3A4 inhibitors (кетоконазол, итраконазол, ритонавир) increase concentration of an amlodipin in a blood plasma stronger, than diltiazem. Amlodipin it is necessary to apply with care in a combination with CYP3A4 inhibitors. However about development of side reactions which are connected with interaction at use of such combination, it was not reported.

Inductors CYP3A4. There is no information on influence of the inductors CYP3A4 on амлодипин. Simultaneous use of an amlodipin and substances which are the inductors CYP3A4 (for example, rifampicin, a St. John's Wort) can lead to decrease in concentration of an amlodipin in a blood plasma therefore it is necessary to apply such combinations with care.

Clinical trials of interactions of drug showed that use of a bitsimetidin, antacids with the content of aluminum or magnesium and a sildenafil do not influence pharmacokinetics of an amlodipin.

Dantrolen (infusions). At animals ventricular fibrillations with a lethal outcome and a cardiovascular collapse which were associated with a hyperpotassemia, after use of verapamil and a dantrolen intravenously were observed. Due to the risk of development of a hyperpotassemia it is recommended to avoid use of blockers of calcium channels, such as амлодипин, to patients, inclined to a malignant hyperthermia, and at treatment of a malignant hyperthermia.

Influence of an amlodipin on other medicines. Hypotensive effect of an amlodipin potentsiirut hypotensive effect of other anti-hypertensive means.

Clinical trials of interaction of drug showed what амлодипин does not influence pharmacokinetics of an atorvastatin, digoxin, ethanol (alcohol), warfarin and cyclosporine.

Contraindications:

– The known hypersensitivity to dihydropyridines, an amlodipin or to any other component of drug.

– Arterial hypotension of heavy degree.

– Shock (including cardiogenic shock).

– Obstruction of the removing path of a left ventricle (for example, a stenosis of an aorta of heavy degree).

- Hemodynamically unstable heart failure after an acute myocardial infarction.

Overdose:

Experience of deliberate overdose of drug is limited.

Overdose symptoms: the available information allows to consider that considerable overdose of drug Aladin will lead to an excessive peripheral vazodilatation and, perhaps, to reflex tachycardia. It was reported about development considerable and, perhaps, long system hypotension, including shock with a lethal outcome.

Treatment: clinically significant hypotension caused by overdose of an amlodipin demands active support of activity of cardiovascular system, including frequent monitoring of functions of heart and breath, a raising of extremities, monitoring of volume of the circulating liquid and urination.

For recovery of a tone of vessels and arterial pressure it is possible to use vasoconstrictive drugs, having convinced of lack of contraindications to their use. Use of calcium of a gluconate can intravenously be useful to leveling of effects of blockade of calcium channels.

In certain cases there can be useful a gastric lavage. Use of absorbent carbon to healthy volunteers within 2 hours after введення 10 mg of an amlodipin considerably reduced the level of its absorption.

As амлодипин to a large extent contacts proteins, the effect of dialysis is insignificant.

Storage conditions:

Period of validity. Aladin of 10 mg – 3 years. Aladin of 5 mg – 2 years. Not to use drug after the termination of the period of validity specified on packaging. To store in original packaging at a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in the blister. On 3 or 5 blisters in a pack.