To statines

General characteristics. Structure:

Active ingredients : 5 mg or 10 mg of an amlodipin (in the form of an amlodipin of a besilat); 10 mg or 10 mg аторвастатин (in the form of an atorvastatin of calcic salt).

Excipients: starch prezhelatinizirovanny, calcium carbonate, sodium of a kroskarmelloz, gipromelloz 2910, silicon dioxide colloid anhydrous, calcium stearate, cellulose microcrystallic, опадрай the II white (85 F) or опадрай the II blue (85 F).

Structure opadry the II white (85 F): the polyvinyl alcohol which is partially hydrolyzed; macrogoal/polyethyleneglycol; talc (E553); titanium dioxide (E171).

Structure opadry the II blue (85 F): the polyvinyl alcohol which is partially hydrolyzed; macrogoal/polyethyleneglycol; talc (E553); titanium dioxide (E171); FD&C (E132) indigo carmine; diamond blue FD&C (E133); ferrous oxide yellow (E172).

The combined drug used for treatment of the combined serdechnoyososudisty diseases (arterial hypertensia / stenocardia and a dislipidemiya).

Pharmacological properties:

Pharmacodynamics. Pharmacological effect of drug is caused by properties of the components which are its part. Amlodipin renders hypotensive and anti-anginal effects. The mechanism of hypotensive action of an amlodipin is caused by the direct weakening impact on unstriated muscles of vessels. 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 resistance of vessels, reduces an afterload by heart, reduces the need of a myocardium for oxygen.

Atorvastatin hypolipidemic means from group of statines. Reduces the level of the general cholesterol, cholesterol of lipoproteins of low density, apolipoprotein B and triglycerides; causes increase in level of cholesterol of lipoproteins of high density and A. Dozozavisimo's apolipoprotein reduces the level of lipoproteins of low density at patients with the homozygous hereditary hypercholesterolemia steady against therapy with other hypolipidemic medicines.

Reduces risk of development of ischemic complications (including development of death from a myocardial infarction), risk of repeated hospitalization concerning the stenocardia which is followed by symptoms of ischemia of a myocardium. Has no cancerogenic and mutagen effect. The therapeutic effect is reached in 2 weeks after the beginning of therapy, reaches a maximum in 4 weeks and remains during the entire period of treatment.

Indications to use:

To statines appoint to patients, которьм simultaneous treatment amlodipiny and atorvastatiny is recommended.

Amlodipin. Arterial hypertension: Amlodipin is shown for treatment of arterial hypertension. Drug is used as in the form of monotherapy, and by combinations with others anti-anginal or antihypertensives.

Coronary Heart Disease (CHD). Chronic stable stenocardia: Amlodipin is shown for treatment of chronic stable stenocardia. Drug is used as in the form of monotherapy, and by combinations with others anti-anginal and antihypertensives.

Vasospastic stenocardia (Printsmetal's stenocardia or alternative stenocardia): Amlodipin is shown for treatment confirmed or at suspicion of vasospastic stenocardia. Drug is used as in the form of monotherapy, and by combinations with other anti-anginal means.

Angiographically the confirmed disease of coronary arteries (DCA): to patients from recently angiographically documentary BKA and without heart failure or with an indicator of fraction of emission <40% амлодипин it is shown for reduction of risk of hospitalization concerning stenocardia and reduction of risk of the procedure of revascularization.

Atorvastatin. Due to the increased risk of development of an atherosclerotic vascular disease at a hypercholesterolemia it is recommended to apply аторвастатин at persons with many risk factors. It is recommended to carry out treatment by medicines at decrease in the answer to the medical diet directed to decrease in saturated fats and cholesterol and also in case of insufficiency of other non-drug methods. At patients with coronary insufficiency or many risk factors of development of coronary insufficiency, treatment by Statinam's component - atorvastatiny can be begun along with a medical diet.

Atorvastatin is recommended to apply for prevention of cardiovascular diseases for:

· decrease in risk of a myocardial infarction,

· decrease in risk of a stroke,

· decrease in risk of implementation of the procedure of revascularization and stenocardia.

At patients with diabetes of the 2nd type without clinical manifestations of coronary insufficiency with several risk factors of coronary insufficiency (for example, a retinopathy, an albuminuria, smoking or hypertensia), аторвастатин it is shown for:

· decrease in risk of a myocardial infarction

· decrease in risk of a stroke

At patients with clinical signs of coronary insufficiency аторвастатин it is shown for:

· decrease in risk of not fatal myocardial infarction

· decrease in risk of a fatal and not fatal stroke

· decrease in risk of implementation of the procedure of revascularization

· decrease in risk of hospitalization at congestive heart failure

· decrease in risk of development of stenocardia 

Heterozygous hereditary and not hereditary hypercholesterolemia: Atorvastatin is shown as addition to a diet for decrease in the increased level of the general cholesterol, LPNP, apolipoprotein B and triglycerides, and also for increase in LPVP at patients with primary hypercholesterolemia (heterozygous hereditary and not hereditary) and with the mixed dislipidemiya (type of Pa and lib on Fredrikson's classification);

The increased level of triglycerides in blood serum: Atorvastatin is shown in a combination with a diet for decrease in the increased level of triglycerides in blood serum (type IV on Fredrikson's classification);

Primary disbetalipoproteinemiya: Atorvastatin is shown for treatment of patients with primary disbetalipoproteinemiya at whom the diet does not give adequate effect;

Homozygous hereditary hypercholesterolemia: Atorvastatin is shown for decrease in the increased level of the general cholesterol and LPNP at patients with a homozygous hereditary hypercholesterolemia in a combination with other medicines lowering the level of lipids (for example, аферез to LPNP), or at impossibility of performing such treatment;

Use for children: Atorvastatin is shown as addition to a diet for decrease in level of the general cholesterol, LPNP and apolipoprotein B at boys and at girls is after menarche of 10-17 years with a heterozygous hereditary hypercholesterolemia in cases when after use of a dietotherapy the following indicators remain:

· the LPNP level remains> 190 mg/dl or

· the LPNP level remains> 160 mg/dl and

· a prematurity of cardiovascular diseases in the family anamnesis or

· two and more risk factors of development of cardiovascular diseases in children.

The research of an antidislipidemichesky component of Statinam at excess of chylomicrons (the I and V type on Fredrikson's classification) was not conducted.

Route of administration and doses:

For treatment of hypertensia/stenocardia and a lipidemia Statinam's dose is selected individually, considering efficiency and portability of each component of medicine. Statinam's tablets are indivisible, and cannot be used during titration of a dose of an amlodipin, since 2,5 mg. In need of titration of a dose of an amlodipin, since 2,5 mg, or reception of an atorvastatin in the dose exceeding 10 mg it is recommended to apply monocomponent medicines: амлодипин and аторвастатин in the corresponding dosages.

Amlodipin (arterial hypertension or stenocardia). At treatment of hypertensia the recommended initial dose of an amlodipin makes 5 mg of 1 times a day inside. The maximum dose - 10 mg of 1 times a day. At patients of low growth, a brittle constitution, advanced age, at patients with a liver failure the initial dose can make 2,5 mg of 1 times a day. The same dose can be applied when using an amlodipin in a combination with other antihypertensives.

The dose is adjusted depending on a condition of the patient. On average the period of selection of a dose takes 7-14 days in order that the doctor could estimate in full the answer of the patient to each level of a dose. Selection can be carried out also for shorter period at frequent assessment of a condition of the patient.

For treatment of chronic stable or vasospastic stenocardia the recommended dose of an amlodipin makes 5-10 mg. Lower dose is applied at elderly people and at patients with a liver failure. For achievement of adequate effect at most of patients the required dose makes 10 mg.

For patients with an atherosclerotic heart trouble the recommended range of doses makes 5-10 mg of 1 times a day. In clinical tests to most of patients appointed 10 mg. 

Use for children: At children at the age of 6-17 years the effective hypotensive dose of an amlodipin makes 2,5-5 mg/days. The dose more than 5 mg at children was not investigated.

Atorvastatin (Lipidemia). A lipidemia (heterozygous hereditary and not hereditary) and the mixed dislipidemiya (types of Pa and P on Fredrikson's classification)

The recommended initial dose of an atorvastatin makes 10-20 mg of 1 times a day. In need of considerable decrease in LPNP (more than 45%) treatment it is possible to begin with a dose 40 mg of 1 times a day. Atorvastatin apply in the range of doses - 10-80 mg of 1 times a day. Atorvastatin it is possible to appoint at any time, meal does not exert impact on medicine. The initial and supporting doses of an atorvastatin are selected individually depending on problems of therapy and the answer of the patient. After an initiation of treatment and/or titration atorvastatiny it is necessary to analyze the level of lipids each 2-4 weeks, then to carry out correction of a dose.

The heterozygous hereditary hypercholesterolemia at children (10-17 years) the Recommended initial dose of an atorvastatin makes 10 mg/days, the maximum recommended dose - 20 mg/days (doses over 20 mg were not studied at this population of patients). The dose should be selected individually depending on the recommended treatment purpose. Change of a dose it is necessary to spend bucketed 4 weeks or more.

Homozygous hereditary hypercholesterolemia. The dose of an atorvastatin at patients with a homozygous hereditary hypercholesterolemia makes 10-80 mg/days Atorvastatin apply as addition to other courses of treatment allowing to reduce the level of lipids (for example, аферез LPNP), and also at impossibility to use such courses of treatment.

The accompanying treatment reducing the level of lipids. Atorvastatin it is possible to apply in a combination with sekvestrant of bile acids. It is necessary to watch myopathy symptoms at the patients who are on a course of treatment statines and fibrata.

Use for patients with a renal failure. Diseases of kidneys do not exert impact on concentration of an atorvastatin in a blood plasma, and also on decrease in LPNP atorvastatiny. Thus, correction of a dose at patients with a renal failure is not carried out.

Use in a combination with other medicines (with cyclosporine, klaritromitsiny, with ritonaviry in a combination with sakvinaviry and with lopinaviry in a combination with ritonaviry)

At use in a combination with cyclosporine the daily dose of an atorvastatin has to make 10 mg. At the patients accepting кларитромицин, итраконазол and at the HIV-positive patients who are on treatment ritonaviry and sakvinaviry or lopinaviry in a combination with ritonaviry if the dose of an atorvastatin exceeds 20 mg, it is necessary to carry out clinical assessment of a condition of the patient which will allow to provide a safe dose.

To statines. Statines can replace with separate medicines (амлодипин and аторвастатин). Patients can appoint an equivalent dose of Statinam, and for achievement of additional anti-anginal action, lowerings of arterial pressure or decrease in level of lipids are shown the increased quantities of an amlodipin, an atorvastatin or both components.

Statines can apply as additional therapy at patients who already are on treatment by one of drug components. As initial therapy on one indicator and for continuation of treatment on another, the initial dose of Statinam is chosen for continuation of use of already used component, and apply the recommended initial dose to the second component.

 To statines apply to initial treatment of patients with a lipidemia and hypertensia or stenocardia. A basis for the recommended initial dose of Statinam is the corresponding combination of recommendations for monotherapy. The maximum daily dose for Statinam's components makes 10 mg of an amlodipin, and an atorvastatin - 80 mg.

Features of use:

Skeletal muscles. At reception of the tablets containing аторвастатин and амлодипин the exceptional cases of a rabdomioliz with an acute renal failure and the subsequent myoglobinuria caused atorvastatiny are known. Risk factor for development of a rabdomioliz is existence of a renal failure. Such patients require more careful observation of a condition of skeletal muscles.

Atorvastatin, as well as other statines, in rare instances can lead to development of a myopathy, the shown muscle pain or muscular weakness in combination with increase in level of a kreatinfosfokinaza (KFK) more than by 10 times from upper threshold value. Combined use of higher doses of an atorvastatin with drugs, such as cyclosporine and strong inhibitors of CYP3A4 cytochrome (for example, klaritromitsiny, itrakonazoly and HIV protease inhibitor) increases risk of development of a myopathy / рабдомиолиза.

Each patient with a diffusion mialgiya, muscle pain, weakness or substantial increase of KFK needs to be inspected on existence of a myopathy. Because of danger of development of a myopathy at reception of statines which Statinama who is a part аторвастатин treats patients is recommended to report immediately about inexplicable muscle pains, morbidity or weakness, especially if they are followed by an indisposition or fever.

Patients with an acute myopathy and having risk factors contributing to development of a renal failure with the subsequent rabdomioliz (for example, a heavy acute infection, arterial hypotension, serious operations, injuries, heavy metabolic, endocrine and electrolytic disturbances and uncontrollable spasms) need to interrupt or stop administration of drug temporarily.

Liver failure. Statines including аторвастатин and also other drugs reducing the level of lipids are capable to cause biochemical abnormal liver functions. It is recommended to measure indicators of function of a liver to and in 12 weeks after an initiation of treatment, at any increase in a dose of drug, and also periodically (for example, time in half a year). Change of level of liver enzymes usually happens within the first 3 months after the beginning of reception of the atorvastatin which is Statinam's part. It is necessary to watch patients at whom increase in level of transaminase is noted before disappearance of disturbances. If the increased ALT or ACT level remains (more than by 3 times from upper threshold value) it is recommended to lower a dose of drug or to stop reception.

Liver disease in an active stage or the inexplicable constant increased level of activity of transaminases are a contraindication to Statinam's use.

Progressirovansh of stenocardia and/or myocardial infarction. Progressing of stenocardia and an acute myocardial infarction can develop after the beginning of increase in a dose of an amlodipin, especially at patients with a serious obstructive disease of a coronary artery.

Hypotension. Development of symptomatic hypotension is possible, especially patients with the expressed stenosis have aortas. Due to the selection of a dose starting with minimum, development of acute hypotension is improbable.

Withdrawal of beta-blockers. Amlodipin who is Statinam's part is not a beta-blocker and therefore cannot prevent development of a withdrawal of beta-blockers; at such withdrawal it is necessary to reduce a beta-blocker dose gradually.

Endocrine function. Atorvastatin, as well as other statines influences synthesis of cholesterol and can theoretically reduce the level of hormones of adrenal glands and/or sex steroid hormones. Clinical trials showed what атровастатин does not reduce the main level of cortisol in plasma and has no negative effect on a reserve of adrenal glands. Effect of statines on male fertility was not studied on enough patients. Effects if those are available, on pituitary and gonadal system at women in the period of a premenopauza are unknown. It is necessary to be careful at purpose of statines with drugs which can lower the level or activity of endogenous steroid hormones, such as кетоконазол, Spironolactonum and Cimetidinum.

Influence on ability to driving of motor transport and to control of potentially dangerous mechanisms: during treatment it is necessary to be careful during the driving of motor transport and occupation potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Side effect of drug is caused by pharmacological properties of each of the components which are its part. Further the undesirable reactions known now caused by each of active components of drug are given. As the frequency of side reactions it is understood: frequent (> 1%), infrequent (<1%), rare (<0,1%), very rare (<0,01%).

Amlodipin.

From cardiovascular system: often - peripheral hypostases (anklebones and feet), heartbeat; infrequently - excessive decrease in the ABP, orthostatic hypotension, a vasculitis; seldom - development or aggravation of heart failure; very seldom - disturbances of a rhythm (bradycardia, ventricular tachycardia, atrial fibrillation), a myocardial infarction, thorax pain, migraine.

From a nervous system: often - a headache, dizziness, increased fatigue, drowsiness; infrequently - an indisposition, a syncope, an adynamy, a hypesthesia, paresthesias, peripheral neuropathy, a tremor, sleeplessness, emotional lability, unusual dreams, nervousness, a depression, alarm; seldom - spasms, apathy, agitation; very seldom - an ataxy, amnesia.

From the alimentary system: often - nausea, abdominal pain; infrequently - vomiting, change of the mode of defecation (including a lock, a meteorism), dyspepsia, diarrhea, anorexia, dryness in a mouth, 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 bodies of a hemopoiesis: very seldom - a Werlhof's disease, a leukopenia, thrombocytopenia.

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

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

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

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

Others: infrequently - an alopecia, a ring in ears, a gynecomastia, increase/decrease in body weight, a vision disorder, a diplopia, accommodation disturbance, a xerophthalmia, conjunctivitis, eye pain, a food faddism, a fever, nasal bleeding, the increased sweating; seldom - dermatitis; very seldom - a cold clammy sweat, a parosmiya, disturbance of a xanthopathy, a hyperglycemia.

Atorvastatin.

From a nervous system: often - sleeplessness, a headache, an asthenic syndrome; infrequently - an indisposition, dizziness, amnesia, paresthesia, peripheral neuropathy, a hypesthesia.

From the alimentary system: often - nausea, diarrhea, pain in a stomach, dyspepsia, a lock, a meteorism; infrequently - vomiting, anorexia, hepatitis, pancreatitis, holestatitchesky jaundice.

From a musculoskeletal system: often - a mialgiya; infrequently and seldom - a dorsodynia, myotonia, a miositis, a myopathy, an arthralgia, рабдомиолиз.

Allergic reactions: infrequently - urticaria, an itch, skin rash, an anaphylaxis, violent rash, a polymorphic exudative erythema, a toxic epidermal necrolysis (Lyell's disease), a malignant exudative erythema (Stephens's syndrome - Johnson).

From a metabolism: infrequently - a hypoglycemia, a hyperglycemia, increase in activity of a serumal kreatininfosfokinaza.

From bodies of a hemopoiesis: infrequently - thrombocytopenia. Other: infrequently - impotence, peripheral hypostases, increase in body weight, pain in a breast, a secondary renal failure, an alopecia, a sonitus, exhaustion.

Interaction with other medicines:

The pharmacokinetics of an amlodipin at a combination therapy with atorvastatiny does not change.

Inhibitors of microsomal enzymes of a liver can increase concentration of an amlodipin in plasma, strengthening risk of development of side effects, and inductors of microsomal enzymes of a liver - to reduce.

Unlike other blockers of slow calcium channels, clinically significant interaction of an amplodipin with non-steroidal anti-inflammatory drugs, especially indometacin is not noted.

Thiazide and "loopback" diuretics, beta adrenoblockers, verapamil, APF inhibitors and nitrates strengthen anti-anginal or hypotensive effects of an amlodipin. The drugs Sa2 + can reduce effect of blockers of slow calcium channels. Antiviral means (ритонавир) increase plasma concentration of blockers of slow calcium channels, including an amlodipin. Neuroleptics and изофлуран - strengthening of hypotensive action of derivatives of dihydropyridine. 

At the co-administration of cyclosporine, fibrat, erythromycin, a klaritromitsin, immunodepressive, antifungal medicines (relating to azoles) and niacinamide concentration of an atorvastatin in plasma (and risk of emergence of a myopathy) raises.

At simultaneous use with erythromycin (on 500 mg 4 times a day) or klaritromitsiny (on 500 mg 2 times a day) increase in concentration of an atorvastatin in a blood plasma is noted.

Antacids reduce concentration of an atorvastatin by 35% (influence on the content of LPNP cholesterol does not change).

At simultaneous use of an atorvastatin (on 10 mg of 1 times a day) and azithromycin (on 500 mg of 1 times a day) concentration of an atorvastatin in plasma does not change. Clinically significant interaction is not noted at simultaneous use with warfarin, Cimetidinum, phenazone.

Simultaneous use of an atorvastatin with the inhibitors of proteases known as CYP3A4 cytochrome inhibitors, is followed by increase in concentration of an atorvastatin in plasma (at simultaneous use with erythromycin Stakh of an atorvastatin increases by 40%).

At use of digoxin in a combination with atorvastatiny in a dose of 80 mg/days concentration of digoxin increases approximately by 20%.

Increases concentration (at appointment with atorvastatiny in a dose of 80 mg/days) the oral contraceptives containing Norethisteronum for 30% and ethinylestradiol for 20%. The hypolipidemic effect of a combination with kolestipoly surpasses that for each drug separately, despite decrease in concentration of an atorvastatin by 25% at its simultaneous use with kolestipoly.

Simultaneous use with the medicines reducing concentration of endogenous steroid hormones (including Cimetidinum, ketokonazoly, Spironolactonum), increases risk of decrease in endogenous steroid hormones (it is necessary to be careful).

At use of digoxin in a combination with atorvastatiny in a dose of 80 mg/days concentration of digoxin increases by 20%.

Contraindications:

Hypersensitivity, active disease of a liver or permanent increase in activity of "hepatic" enzymes (more than by 3 times) not clear etiology, the expressed arterial hypotension (the GARDEN less than 90 mm hg), use for the women of reproductive age who are not using adequate methods of contraception; pregnancy, the lactation period, age up to 18 years.

With care: Arterial hypotension, an aortal stenosis, chronic heart failure of not ischemic etiology (the III-IV class on NYHA classification), an acute myocardial infarction (and within 1 month after), a hypertrophic subaortic stenosis, a sick sinus syndrome, an alcoholism and/or diseases of a liver (in the anamnesis), advanced age.

Overdose:

Symptoms: the excessive peripheral vazodilatation leading to reflex tachycardia; the expressed and permanent decrease in the ABP, including with development of shock and a lethal outcome. Besides, pains in a liver, an acute renal failure can also be probable symptoms; at prolonged use a myopathy and рабдомиолиз.

Treatment: absorbent carbon at once or during 2 h after reception, a gastric lavage, giving of sublime situation to extremities, control of OTsK, a diuresis, indicators of function of heart and lungs, maintenance of function of cardiovascular system, vasoconstrictive drugs, intravenously a gluconate of Sa2 + (for elimination of effects of blockade of channels Sa2+). Atorvastatin substantially contacts proteins of a blood plasma owing to what, the hemodialysis is inefficient. At development of a myopathy, with the subsequent rabdomioliz and an acute renal failure (seldom) - immediate drug withdrawal and administration of diuretic and solution of Natrii hydrocarbonas. Rabdomioliz can lead to development of a hyperpotassemia which elimination requires intravenous administration of calcium chloride or a gluconate of calcium, infusion of glucose with insulin, use of ion exchangers of potassium ions or, in hard cases of carrying out a hemodialysis.

Storage conditions:

In the place protected from moisture and light at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity 2 years. Not to use after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in a blister strip packaging. Three blister strip packagings together with the application instruction in a pack from a cardboard.