Aktalipid

General characteristics. Structure:

Active agent: симвастатин 10 mg, 20 mg or 40 mg.
Excipients: lactoses monohydrate, cellulose microcrystallic, povidone, sodium of a kroskarmelloz, talc, ascorbic acid, anhydrous citric acid, butylhydroxyanisole, magnesium stearate.
Structure of a cover: gipromelloza, titanium dioxide, macrogoal, ferrous oxide yellow, ferrous oxide red.
Description: biconvex, round, beige color of a tablet, coated.

Pharmacological properties:

Pharmacodynamics. The hypolipidemic drug received in the synthetic way from Aspergillus tereus fermentation product is an inactive lactone, in an organism is exposed to hydrolysis with formation of hydroxyacid derivative. The active metabolite inhibits 3-gidroksi-3-metilglyutaril-KOA-reduktazu (GMG-KOA-reduktazu), the enzyme catalyzing initial reaction of formation of a mevalonat from GMG-KOA. As transformation GMG-KOA in мевалонат represents an early stage of synthesis of cholesterol, use of a simvastatin does not cause accumulation in an organism of potentially toxic sterol. GMG-KOA it is easily metabolized to atsetil-KOA which participates in many processes of synthesis in an organism.
Causes decrease in contents in a blood plasma of triglycerides (TG), lipoproteids of the low density (LPNP) and lipoproteids of very low density (LPONP) and the general cholesterol (in cases of heterozygous family and single forms of a hypercholesterolemia, at the mixed lipidemia when the increased content of cholesterol is risk factor).
Increases the maintenance of lipoproteids of the high density (LPVP) and reduces a ratio of LPNP/LPVP and the general cholesterol / LPVP.
The beginning of manifestation of effect - in 2 weeks from the beginning of reception, the maximum therapeutic effect is reached in 4-6 weeks. Action remains at treatment continuation, at the therapy termination the content of cholesterol gradually is returned to initial level.

Pharmacokinetics. Absorption - high. After intake the maximum concentration (TCmax) in a blood plasma is reached in 1,3 – 2,4 hours and decreases by 90% in 12 hours.
Communication with proteins of a blood plasma – 95%.
It is metabolized in a liver, has "effect of the first passing" through a liver (it is hydrolyzed with formation of active derivative - beta hydroxyacids, both other active and inactive metabolites are found). The elimination half-life of active metabolites makes 1,9 hours.
It is removed preferential with a fecal masses (60%) in the form of metabolites.

Indications to use:

Hypercholesterolemia:
• primary hypercholesterolemia (IIA and IIb type) at inefficiency of a dietotherapy with the low content of cholesterol and other non-drug actions (an exercise stress and decrease in body weight) at patients with the increased risk of developing of coronary atherosclerosis;
• the combined hypercholesterolemia and the gipertriglitseridemiya which are not adjusted by a special diet and an exercise stress.

Coronary heart disease:
• for prevention of a myocardial infarction, for reduction of risk of death, reduction of risk of cardiovascular disturbances (a stroke or tranzitorny ischemic attacks), delay of progressing of atherosclerosis of coronary vessels, reduction of risk of procedures of revascularization.

Route of administration and doses:

Before an initiation of treatment drug sick it is necessary to appoint a standard, hypocholesteric diet which needs to be observed also during treatment.
Drug is used in 1 times a day in the evening, washing down with enough water.
Time of administration of drug should not be combined with meal.
The recommended dose for treatment of a hypercholesterolemia varies from 10 to 80 mg of 1 times a day in the evening. The recommended initial dose of drug for patients with a hypercholesterolemia makes 10 mg.
The maximum daily dose - 80 mg.
It is necessary to carry out change (selection) of a dose at an interval of 4 weeks. At most of patients the optimum effect is reached at administration of drug in doses to 20 mg a day.
At patients with a homozygous hereditary hypercholesterolemia the recommended daily dose of drug makes 40 mg of 1 times a day in the evening or 80 mg in three steps (20 mg in the morning, 20 mg in the afternoon and 40 mg in the evening).
For treatment of patients with an ischemic disease (ischemic heart disease) or high risk of development of an ischemic heart disease effective doses of Aktalipid make 20-40 mg a day. Therefore the recommended initial dose at such patients - 20 mg a day. Changes (selection) of a dose should be carried out bucketed in 4 weeks, if necessary it is possible to increase a dose to 40 mg a day. If the maintenance of LPNP less than 75 mg/dl (1,94mmol/l), the content of the general cholesterol – less than 140 mg/dl (3,6 mmol/l) a dose of drug it is necessary to reduce.
At patients of advanced age and at patients with the easy or moderately expressed degree of a renal failure (clearance of creatinine less than 30 ml/min.) or receiving cyclosporine, даназол, gemfibrozit or other fibrata (except a fenofibrat), Niacinum in lipidsnizhayushchy doses (≥ 1 g/days) in a combination with simvastatiny, most recommended dose of drug should not exceed 10 mg a day.
For the patients accepting Amiodaronum or verapamil along with drug, the daily dose should not exceed 20 mg.

Features of use:

At the beginning of therapy by Aktalipid perhaps passing increase in level of "hepatic" enzymes. Before therapy and further it is regularly necessary to conduct a research of function of a liver (to control activity of "hepatic" transaminases each 6 weeks within the first 3 months, then each 8 weeks within the remained first year, and then time in half a year), also at increase in doses it is necessary to carry out the test for definition of function of a liver. At increase in a dose to 80 mg it is necessary to carry out the test each 3 months. At permanent increase in activity of transaminases (by 3 times in comparison with initial level) administration of drug should be stopped.
Aktalipid, as well as other inhibitors of GMG-KOA-reduktazy, it is not necessary to apply at the increased risk of development of a rabdomioliz, a renal failure (against the background of a heavy acute infection, arterial hypotension, the planned big surgery, injuries, heavy metabolic disturbances).
Cancellation of hypolipidemic means during pregnancy has no significant effect on results of treatment of primary hypercholesterolemia.
Because inhibitors of GMG-KOA-reduktazy slow down cholesterol synthesis, and cholesterol and other products of its synthesis play an essential role in fetation, including synthesis of steroids and cellular membranes, симвастатин can make an adverse effect on a fruit at appointment to his pregnant women (women of childbearing age have to avoid conception during treatment by drug). If in the course of treatment there occurred pregnancy, drug has to be cancelled, and the woman is warned about possible danger to a fruit. Use of drug is not recommended to women of childbearing age, not using contraceptive means.
At patients with the lowered function of a thyroid gland is (hypothyroidism) or in the presence of some diseases of kidneys (a nephrotic syndrome) at increase in level of cholesterol it is necessary to carry out therapy of the cornerstone disease at first.
Aktalipid with care appoint to persons who abuse alcohol and/or have in the anamnesis of a disease of a liver.
Prior to the beginning of and during treatment the patient has to be on a hypocholesteric diet.
The concomitant use of grapefruit juice and drug can strengthen degree of manifestation of by-effects therefore it is necessary to avoid their concomitant use.
Aktalipid is not shown when there is a gipertriglitseridemiya I, IV, V types.
Treatment by drug can cause the myopathy leading to a rabdomioliz and a renal failure. The risk of developing of this pathology increases at the patients receiving along with drug one or a little from the following medicines: fibrata (gemfibrozit, фенофибрат), cyclosporine, нефазадон, macroleads (erythromycin, кларитромицин), antifungal means from group of "azoles" (кетоконазол, интраконазол) and inhibitors of HIV proteases (ритонавир). The risk of development of a myopathy increases also at patients with a heavy renal failure.
All patients beginning therapy with drug and also patients who need to increase a drug dose have to be warned about possibility of a myopathy and need of the immediate address to the doctor in case of developing of inexplicable pains, morbidity in muscles, slackness or muscular weakness, especially if it is followed by an indisposition or fever. Therapy by drug has to be immediately stopped if the myopathy is diagnosed or is supposed.
For diagnosing of development of a myopathy it is recommended to take measurements of size KFK regularly.
At treatment by drug increase of maintenance of serumal KFK is possible that should be considered at differential diagnosis of pains behind a breast. As criterion of drug withdrawal serves increase in maintenance of KFK in blood serum more than by 10 times of rather upper bounds of norm. At patients with a mialgiya, a myasthenia and/or the expressed increase in activity of KFK treatment with drug is stopped.
Drug is effective both in the form of monotherapy, and in combination with sekvestrant of bile acids.
In case of the admission of the current dose drug needs to be accepted as soon as possible. If came time of reception of the following dose, a dose not to double.
To patients with a heavy renal failure treatment is carried out under control of function of kidneys.
Duration of use of drug is defined by the attending physician individually.

Driving of the car and work with mechanisms

About adverse influence of drug on ability to manage motor transport and work with mechanisms it was not reported.

Side effects:

Alimentary system: abdominal pains, a lock, a meteorism, nausea, diarrhea, pancreatitis, vomiting, hepatitis, increase in activity of "hepatic" enzymes, an alkaline phosphokinase and kreatinfosfokinaza (KFK) are possible.
Nervous system and sense bodys: asthenic syndrome, dizziness, headache, sleeplessness, muscular spasms, paresthesias, peripheral neuropathy, sight vagueness, disturbance of flavoring feelings.
Allergic and immunopathological reactions: Quincke's disease, rheumatic polimialgiya, vasculitis, thrombocytopenia, increase SOE, fever, arthritis, urticaria, photosensitization, dermahemia, inflows, asthma, volchanochnopodobny syndrome, eosinophilia.
Dermatological reactions: seldom skin rash, itch, alopecia, dermatomyositis.
From a musculoskeletal system: mialgiya, myopathy, muscular spasms, weakness, рабдомиолиз.
Others: anemia, heartbeat, an acute renal failure (owing to a rabdomioliz), decrease in a potentiality.

Interaction with other medicines:

Cytostatics, antifungal means (кетоконазол, итраконазол), fibrata, high doses of niacin, immunodepressants, erythromycin, кларитромицин, телитромицин, HIV protease inhibitors, нефазодон increase risk of development of a myopathy.
Cyclosporine or даназол: the risk of development of a myopathy / рабдомиолиза increases at joint purpose of cyclosporine or a danazol with high doses of a simvastatin.
Other hypolipidemic means capable to cause development of a myopathy: the risk of development of a myopathy increases at joint purpose of other hypolipidemic means which are not powerful CYP3A4 inhibitors, but capable to cause a myopathy in the conditions of monotherapy. Such as gemfibrozit also other fibrata (except a fenofibrat), and also Niacinum (niacin) in a dose ≥ 1,0 g a day.
Amiodaronum and verapamil: the risk of development of a myopathy increases at joint reception of Amiodaronum or verapamil with high doses of a simvastatin.
Diltiazem: the risk of development of a myopathy slightly increases at patients of 80 mg accepting diltiazem along with drug in a dose.
Simvastatin exponentiates effect of peroral anticoagulants (for example, фенпрокумон, warfarin) and increases risk of developing of bleedings that demands need of monitoring procedure of indicators of coagulability of blood prior to treatment, and is also rather frequent during an initial stage of therapy. As soon as the stable level of an indicator of a prothrombin time or the International Normalized Relation (INR) is reached, its further control should be carried out bucketed, recommended for the patients receiving therapy by anticoagulants. At change of a dosage or the termination of reception of a simvastatin it is also necessary to carry out control of a prothrombin time or MNO according to the above scheme.
Therapy simvastatiny does not cause changes of a prothrombin time and risk of bleedings in the patients who are not accepting anticoagulants.
Increases digoxin level in a blood plasma.
Colestyraminum and колестипол reduce bioavailability (administration of drug is possible in 4 hours after reception of the specified medicines, at the same time the additive effect is noted).
Juice of grapefruit contains one or more components which inhibit CYP3A4 and can increase concentration in a blood plasma of the means which are metabolized CYP3A4. Increase in activity of inhibitors of GMG-KOA-reduktazy after the use of 250 ml of grapefruit juice in day is minimum and has no clinical value. However consumption of bigger volume of juice (more than 1 l) at reception of a simvastatin considerably increases the level of the inhibiting activity concerning GMG-KOA-reduktazy in a blood plasma. In this regard it is necessary to avoid consumption of grapefruit juice in large numbers during administration of drug.

Contraindications:

• Hypersensitivity to a simvastatin or to other components of drug (including a hereditary lactose intolerance), and also to other drugs of a statinovy row (GMG-KOA-reduktazy inhibitors) in the anamnesis;
• liver diseases in an active phase, permanent increase in activity of "hepatic" enzymes of not clear etiology;
• diseases of skeletal muscles (myopathy);
• age up to 18 years (efficiency and safety are not established).

With care drug is appointed the patient abusing alcohol, to patients after organ transplantation which carries out treatment by immunodepressants (in connection with the increased risk of emergence of a rabdomioliz and a renal failure); at states which can lead to development of the expressed insufficiency of function of kidneys, such as arterial hypotension, acute infectious diseases of a heavy current, the expressed metabolic and endocrine disturbances, disturbances of water and electrolytic balance, surgical interventions (including dental) or injuries; to patients with the raised or lowered tone of skeletal muscles of not clear etiology; epilepsies.

Pregnancy and period of a lactation

Drug should not be used during pregnancy. There are several messages on development of anomalies in newborns which mothers accepted симвастатин.
The women of childbearing age accepting drug have to avoid conception. If in the course of treatment there occurred pregnancy, drug has to be immediately cancelled, and the woman is warned about possible danger to a fruit.
Data on allocation of a simvastatin with maternal milk are absent. In need of Aktalipid's appointment during feeding by a breast it is necessary to consider that many medicines are allocated with breast milk, and there is a threat of development of heavy reactions therefore feeding by a breast during administration of drug is not recommended.

Overdose:

In one of the known cases of overdose (most accepted dose of 450 mg) of specific symptoms it was not revealed.
Treatment: to cause vomiting, absorbent carbon. Symptomatic therapy. It is necessary to control function of a liver and kidneys, the KFK level in blood serum.
At development of a myopathy with rabdomiolizy and an acute renal failure (rare, but heavy side effect) it is necessary to stop immediately administration of drug and to enter to the patient diuretic and sodium bicarbonate (intravenous infusion). If necessary the hemodialysis is shown.
Rabdomioliz can cause a hyperpotassemia which can be eliminated with intravenous administration of calcium chloride or calcium of a gluconate, infusion of glucose with insulin, use of potassium ion exchangers or, in hard cases, by means of a hemodialysis.

Storage conditions:

At a temperature not above 25 °C. To store in the place, unavailable to children! Period of validity 3 years. Drug should not be used after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets, coated, on 10, 20 and 40 mg. On 14 tablets in the blister. On 2 blisters together with the application instruction in a cardboard pack.