Atorvastatin tab n / 40mg film about 30 pieces vertex

Description

Composition
Active substance:
1 tablet contains: atorvastatin calcium trihydrate (calculated as atorvastatin) – 10.00 mg, 20.00 mg, 40.00 mg and 80.00 mg.
Excipients:
Microcrystalline cellulose, lactose monohydrate, calcium carbonate, crospovidone, sodium carboxymethyl starch (sodium starch glycolate), giproloza (hydroxypropyl cellulose), magnesium stearate; film coating: [hypromellose, talc, giproloza (hydroxypropylcellulose), titanium dioxide] or [dry film coating mixture comprising hypromellose (50.0%), talcum (19.6%), giproloza (hydroxypropylcellulose) (19.4% ), titanium dioxide (11.0%)].
Description:
Round biconvex tablets, film-coated white or almost white. The cross-sectional core of a white or nearly white.
Product form:
Tablets, film-coated, 10 mg, 20 mg, 40 mg and 80 mg. 10, 15 or 30 tablets in blisters of PVC film and aluminum foil. 30, 60 or 90 tablets in a bank of high-density polyethylene. 1, 2 or 3 blisters with 10 tablets 1, 2 or 4 blisters 15 tablets, 1, 2 or 3 blisters of 30 tablets or one bank, along with instructions for medical use in a stack of cardboard.
Contraindications
Hypersensitivity to any component of the drug; liver disease in an active stage; increase in “liver” transaminases in the blood plasma of unclear origin by more than 3-fold compared with the upper limit of normal; skeletal muscle disease; lactase deficiency, lactose intolerance, a syndrome of glucose-galactose malabsorption; pregnancy and lactation; age 18 years (insufficient clinical efficacy and safety data for this age group).
C care
Use in patients with alcohol abuse or in patients with a history of liver disease.
Dosage
40 mg
Indications
The primary hypercholesterolemia (heterozygous familial and non-family hypercholesterolemia (type IIa by Fredrickson) combined (mixed) hyperlipidemia (IIa and IIb types according to Fredrickson); disbetalipoproteinemiya (III type according to Fredrickson) (as an adjunct to diet), familial endogenous hypertriglyceridemia (IV type according to Fredrickson), resistant to diet; homozygous familial hypercholesterolemia the lack of effectiveness of diet therapy, and other non-pharmacological treatments, primary prevention of cardiovascular complicated d in patients without clinical evidence of coronary heart disease (coronary heart disease), but having multiple risk factors for its development over the age of 55 years, nicotine dependence, hypertension, diabetes, genetic predisposition, including on the background of dyslipidemia, secondary prevention of cardiovascular vascular complications in patients with coronary artery disease to reduce the overall mortality rate, myocardial infarction, stroke, rehospitalization for angina and the need for revascularization.
Interaction with other drugs
The risk of myopathy with rhabdomyolysis and renal insufficiency during treatment inhibitors of HMG-CoA reductase is increased while the use of cyclosporine, antibiotics (erythromycin, clarithromycin, quinupristin / dalfopristin), HIV protease inhibitors (indinavir, ritonavir), antifungal drugs (fluconazole, itraconazole, ketoconazole), nefazodone. All of these drugs inhibit isoenzyme CYP3A4, which is involved in the metabolism of atorvastatin in the liver.
A similar reaction is possible with simultaneous application of atorvastatin with fibrates and nicotinic acid in a lipid-lowering doses (more than 1 g per day).
While the use of inhibitors of HIV protease inhibitors of hepatitis C, clarithromycin, itraconazole, and care should be taken to use the lowest effective dose of atorvastatin.
Inhibitors of CYP3A4
Since atorvastatin is metabolized isoenzyme CYP3A4, concomitant use of atorvastatin with inhibitors of CYP3A4 isoenzyme may increase atorvastatin plasma concentration. The degree of interaction and potentiating effect determined variability in exposure isoenzyme CYP3A4.
transport protein inhibitors OATR1V1
Atorvastatin and its metabolites are substrates OATR1V1 transport protein. OATR1V1 inhibitors (e.g., cyclosporin) can increase the bioavailability of atorvastatin.
Erythromycin / clarithromycin
With simultaneous application of atorvastatin and erythromycin or clarithromycin, which inhibit the CYP3A4 isozyme, there was an increase atorvastatin plasma concentration.
protease inhibitors
Simultaneous use of atorvastatin with protease inhibitors, known inhibitors of CYP3A4 isoenzyme, accompanied by an increase atorvastatin plasma concentration.
diltiazem
The combined use of atorvastatin 40 mg diltiazem with 240 mg atorvastatin leads to an increase in concentration in the blood plasma.
itraconazole
Simultaneous use of atorvastatin and itraconazole led to an increase atorvastatin plasma concentration.
Grapefruit juice
Because the grapefruit juice contains one or more components which inhibit isozyme CYP3A4, its excessive consumption (more than 1.2 liters per day) may cause an increased concentration of atorvastatin in plasma.
Inducers of CYP3A4
Combined use with atorvastatin isoenzyme inducers of CYP3A4 (e.g., efavirenz, phenytoin or rifampicin) may reduce the concentration of atorvastatin in plasma. Because of the dual mechanisms of interaction with rifampicin (isoenzyme CYP3A4 inducer and an inhibitor of the transport protein OATR1V1 hepatocytes) to the simultaneous use of atorvastatin and rifampicin as atorvastatin delayed after receiving rifampicin significantly reduces the concentration of atorvastatin in plasma.
antacids
With the simultaneous ingestion of atorvastatin and a suspension containing magnesium and aluminum hydroxides, atorvastatin decreases the concentration in the blood plasma.
phenazone
Atorvastatin not affect the pharmacokinetics of phenazone, so interaction with other drugs metabolized by the same enzyme cytochrome not expected.
colestipol
With simultaneous application of colestipol atorvastatin plasma concentration was reduced by about 25%, but the hypolipidemic effect of the combination of atorvastatin and colestipol than that of each drug separately.
Digoxin
In the application of digoxin in combination with atorvastatin 80 mg / day digoxin concentrations increased by approximately 20%, however, these patients should be monitored.
oral contraceptives
With simultaneous use of atorvastatin and oral contraceptive containing ethinyl estradiol and norethisterone, possibly increasing the suction contraceptives and increasing their plasma concentrations. This effect should be considered when selecting an oral contraceptive for a woman taking atorvastatin.
terfenadine
Atorvastatin while applying no clinically significant effect on the pharmacokinetics of terfenadine.
warfarin
Concomitant use of atorvastatin and warfarin may increase the impact of the first days of warfarin on the blood clotting parameters (decrease in prothrombin time). This effect disappears after 15 days, the simultaneous application of these drugs.
amlodipine
With simultaneous use of atorvastatin 80 mg or amlodipine 10 mg atorvastatin pharmacokinetics in the equilibrium state is not changed.
fusidic acid
Cases of rhabdomyolysis in patients treated with atorvastatin and fusidic acid.
colchicine
myopathy cases were reported, while the application of atorvastatin and colchicine. In combination therapy with these agents should be careful.
cimetidine
It has been detected in studying the interaction of atorvastatin with cimetidine evidence of clinically significant interaction.
Other concomitant therapy
Simultaneous use of atorvastatin with drugs that reduce the concentration of endogenous steroid hormones (including cimetidine, ketoconazole, spironolactone), increases the risk of reduction of endogenous steroid hormones (caution).
In clinical studies, atorvastatin used in combination with antihypertensive agents and estrogen that are administered as a replacement therapy; symptoms of clinically significant adverse interactions were observed. interaction studies have not been conducted with specific medications.
Overdose
Overdose cases are not described.
In case of overdose require the following basic events: monitoring and maintenance of vital functions, as well as prevent further absorption of the drug (gastric lavage, activated charcoal or laxatives).
With the development of myopathy and rhabdomyolysis with subsequent acute renal failure drug should be lifted immediately and begin infusion of a diuretic and sodium bicarbonate.
Rhabdomyolysis can cause hyperkalemia, urgently requiring intravenous solution of calcium chloride or calcium gluconate solution, infusion of 5% dextrose (glucose) with insulin use kaliyobmennyh resins.
Because the drug is actively bound to plasma proteins, hemodialysis is not effective.
pharmachologic effect
Pharmacological group:
Lipid-lowering drugs – HMG-CoA reductase.
Pharmacodynamics:
Atorvastatin – selective competitive inhibitor of HMG-CoA reductase, a key enzyme that converts 3-hydroxy-3-methylglutaryl-CoA to mevalonate – precursor steroids, including cholesterol; a synthetic lipid-lowering agent.
In patients with homozygous and heterozygous familial hypercholesterolemia, non-family forms of hypercholesterolemia and mixed dyslipidemia, atorvastatin reduces the concentration of total cholesterol plasma levels (LDL) cholesterol low density lipoprotein (LDL-C) and apolipoprotein B (apo-B), as well as the concentration of lipoproteins very low density (LDL-VLDL) and triglycerides (TG) causes unstable increasing the concentration of high density lipoprotein cholesterol (HDL-Xc).
Atorvastatin decreases the concentration of cholesterol and lipoproteins in the blood plasma by inhibiting HMG-CoA reductase and cholesterol synthesis in the liver and by increasing the number of “liver” LDL receptors on the cell surface leads to increased trapping and catabolism of LDL-C.
Atorvastatin reduces the formation of LDL-C and the number of LDL particles, causes a marked and sustained increase in the activity of LDL-receptors in combination with favorable qualitative changes in LDL particles, but also reduces the concentration of LDL-C in patients with homozygous hereditary familial hypercholesterolemia resistant to therapy other hypolipidemic means.
Atorvastatin in doses ranging from 10 mg to 80 reduces the concentration of total cholesterol by 30-46%, LDL-C at 41-61%, apo-B of 34-50% and TG by 14-33%. Results similar therapy in patients with heterozygous familial hypercholesterolemia, non-family forms of hypercholesterolemia, and mixed hyperlipidemia, including in patients with type 2 diabetes.
In patients with isolated hypertriglyceridemia, atorvastatin reduces the concentration of total cholesterol, LDL-C, LDL-VLDL, apo B, and TG, and increases the concentration of LDL-HDL. Patients with disbetalipoproteinemiey reduces the concentration of cholesterol intermediate-density lipoproteins (LDL-LPPP).
In patients with hyperlipoproteinemia type IIa and IIb according to the classification Fredrickson average value Xc increasing the concentration of HDL in the treatment of atorvastatin (10-80 mg) compared to baseline it is 5,1-8,7% and is independent of dose. There is a significant dose-dependent reduction in the magnitude relations: total cholesterol / HDL-Xc-Xc and LDL / HDL-Xc at 29-44% and 37-55% respectively.
Atorvastatin 80 mg significantly reduced the risk of coronary morbidity and mortality by 16% after 16 weeks of treatment, and the risk of re-hospitalization for angina, accompanied by signs of myocardial ischemia – by 26%. In patients with different initial concentrations of LDL-C (myocardial infarction without Q-wave MI and unstable angina, men and women, in patients younger and older than 65 years) is atorvastatin reduced risk of ischemic complications and mortality.
Reduced blood levels of LDL-C plasma correlates better with a dose of atorvastatin than with its concentration in the blood plasma. The dose is selected taking into account therapeutic effects (see. The section “Method of administration and dose”).
The therapeutic effect is achieved within 2 weeks after initiation of therapy, reaching a peak at 4 weeks and maintained throughout the treatment period.
Pharmacokinetics:
Suction
Atorvastatin is rapidly absorbed after oral administration: time to reach its maximum concentration (TCmax) in plasma reaches a maximum after 1-2 hours. Women atorvastatin maximum concentration (Cmax) is 20% higher, and the area under the curve “concentration-time» (AUC) – 10% lower than in men. The degree of absorption and the plasma concentration increased proportionally with dose. The absolute bioavailability – about 14% and the systemic bioavailability of inhibitory activity against HMG-CoA reductase inhibitors – about 30%. The low systemic bioavailability due to first-pass metabolism in the mucosa of the gastrointestinal tract and / or “primary” through the liver. Ingestion somewhat reduces the rate and extent of absorption of the drug (25% and 9%, respectively, as evidenced by the results of determination of Cmax and AUC), but LDL-C reduction is similar to that when receiving atorvastatin fasting. Despite the fact that after the atorvastatin in the evening its plasma concentration is lower (Cmax and AUC by about 30%) than after ingestion in the morning, lowering the concentration of LDL-C is not dependent on the time of day that take medication.
Distribution
The mean volume of distribution of atorvastatin is about 381 liters. Communication atorvastatin plasma proteins at least 98%. The ratio of atorvastatin concentration in erythrocytes / blood plasma is about 0.25, i.e., Atorvastatin does not penetrate into erythrocytes.
Metabolism
Atorvastatin is largely metabolized with formation of ortho- and paragidroksilirovannyh derivatives, and various products of beta-oxidation. In vitro and ortho paragidroksilirovannye metabolites have an inhibitory effect on HMG-CoA reductase, comparable to that of atorvastatin. The inhibitory activity against HMG-CoA reductase inhibitor of approximately 70% is due to the activity of circulating metabolites. The results of in vitro studies provide evidence to suggest that liver CYP3A4 isozyme plays an important role in the metabolism of atorvastatin. This is confirmed by an increase in the concentration of atorvastatin in human blood plasma, while taking erythromycin, which is an inhibitor of that isoenzyme.
in vitro studies have also shown that atorvastatin is a weak inhibitor of isozyme CYP3A4. Atorvastatin had no clinically significant effect on blood levels of terfenadine plasma, which is metabolized primarily by CYP3A4 isoenzyme, so it is a significant effect on the pharmacokinetics of other substrates of CYP3A4 isoenzyme unlikely.
breeding
Atorvastatin and its metabolites are excreted mainly in the bile after hepatic and / or extrahepatic metabolism (atorvastatin does not undergo pronounced enterohepatic recirculation). The half-life (T1 / 2) is about 14 hours, the inhibitory effect of the drug against HMG-CoA reductase inhibitor of approximately 70% determined by the activity of circulating metabolites and persists for about 20-30 hours due to their presence. After taking the drug inside urinary exhibit less than 2% of the dose of atorvastatin.
Pharmacokinetics in special patient groups
elderly patients
The concentration of atorvastatin in plasma levels in elderly patients (aged> 65 years) is higher (Cmax approximately 40%, the AUC by approximately 30%) than in adults younger patients. Differences in safety or effectiveness of achieving the objectives of lipid-lowering therapy in elderly patients compared with the general population have been identified.
Children
Pharmacokinetics studies have not been conducted in children.
Patients with renal function insufficiency
Renal dysfunction does not affect the concentration of atorvastatin in plasma or its effects on lipid metabolism, in connection with this change the dose in patients with impaired renal function is not required. Atorvastatin is not output during dialysis due to intensive plasma protein binding.
Patients with liver failure
Atorvastatin concentrations are significantly increased (Cmax approximately 16 times, AUC of about 11-fold) in patients with alcoholic liver cirrhosis (class B of Child-Pugh).
Pregnancy and breast-feeding
Use of the drug Atorvastatin is contraindicated during pregnancy and lactation. Women of reproductive age during treatment should use adequate contraception methods. Atorvastatin can be administered to women of childbearing age only when the probability of pregnancy are very low and the patient informed of the potential risk to the fetus during treatment.
It is not known whether atorvastatin is excreted in breast milk. Given the possibility of adverse events in infants, if necessary, the drug should stop breastfeeding.
Conditions of supply of pharmacies
Prescription.
side effects
Classification of the incidence of side effects of the World Health Organization (WHO): very common> 1/10, often by> 1/100 to
special instructions
Before starting therapy with atorvastatin patient must assign a standard hypocholesterolemic diet, which he must comply during the entire treatment period.
When the severe adverse effects of the use of atorvastatin drug should be discontinued.
Effects on the liver
Как и при применении других гиполипидемических средств этого класса, после лечения аторвастатином отмечали умеренное (более чем в 3 раза по сравнению с верхней границей нормы) повышение сывороточной активности «печеночных» трансаминаз АСТ и АЛТ. Повышение активности «печеночных» трансаминаз обычно не сопровождалось желтухой или другими клиническими проявлениями. При снижении дозы аторвастатина, временной или полной отмене препарата активность «печеночных» трансаминаз возвращалась к исходному уровню. Большинство пациентов продолжали прием аторвастатина в сниженной дозе без каких-либо клинических последствий.
До начала терапии, через 6 недель и 12 недель после начала применения препарата Аторвастатин или после увеличения его дозы, а также во время всего курса лечения необходимо контролировать показатели функции печени. Функцию печени следует исследовать также при появлении клинических признаков поражения печени. В случае повышения активности «печеночных» трансаминаз их активность следует контролировать до тех пор, пока она не нормализуется. Если повышение активности АСТ или АЛТ более чем в 3 раза по сравнению с верхней границей нормы сохраняется, рекомендуется снижение дозы или отмена препарата.
Аторвастатин следует применять с осторожностью у пациентов, которые потребляют значительные количества алкоголя и/или имеют в анамнезе заболевание печени. Активное заболевание печени или постоянно повышенная активность «печеночных» трансаминаз в плазме крови неясного генеза являются противопоказанием к применению препарата Аторвастатин.
Действие на скелетные мышцы
У пациентов, получавших аторвастатин, отмечалась миалгия. Диагноз миопатии (боли в мышцах и слабость в сочетании с повышением активности креатинфосфокиназы более чем в 10 раз по сравнению с верхней границей нормы) следует предполагать у пациентов с диффузной миалгией, болезненностью или слабостью мышц и/или выраженным повышением активности КФК. Терапию препаратом Аторвастатин следует прекратить в случае выраженного повышения активности КФК или при наличии подтвержденной или предполагаемой миопатии. Риск миопатии при лечении другими препаратами этого класса повышался при одновременном применении циклоспорина, фибратов, эритромицина, никотиновой кислоты в липидснижающих дозах (более 1 г/сут), нефазодона, некоторых антибиотиков, азольных противогрибковых препаратов, ингибиторов ВИЧ-протеазы. Многие из этих препаратов ингибируют метаболизм, опосредованный изоферментом CYP3A4, и/или транспорт лекарственных средств. Известно, что изофермент CYP3A4 – основной изофермент печени, участвующий в биотрансформации аторвастатина. Назначая препарат Аторвастатин в комбинации с фибратами, эритромицином, иммунодепрессантами, азольными противогрибковыми препаратами или никотиновой кислотой в липидснижающих дозах, следует тщательно взвесить ожидаемую пользу и возможный риск. Следует регулярно наблюдать пациентов с целью выявления болей или слабости в мышцах, особенно в течение первых месяцев лечения и в периоды повышения дозы любого из указанных средств. В случае необходимости комбинированной терапии следует рассмотреть возможность применения указанных препаратов в более низких начальных и поддерживающих дозах. В подобных ситуациях можно рекомендовать периодическое определение активности КФК, хотя такое мониторирование не позволяет предотвратить развитие тяжелой миопатии.
При применении аторвастатина, как и других статинов, описаны редкие случаи рабдомиолиза с острой почечной недостаточностью, обусловленной миоглобинурией. При появлении симптомов возможной миопатии или наличии фактора риска почечной недостаточности на фоне рабдомиолиза (например, тяжелая острая инфекция, артериальная гипотензия, обширное хирургическое вмешательство, травмы, метаболические, эндокринные и водно-электролитные нарушения и неконтролируемые судороги) терапию препаратом Аторвастатин следует временно прекратить или полностью отменить.
При дифференциальном диагнозе болей за грудиной следует учитывать возможность увеличения сывороточной активности КФК при применении препарата Аторвастатин.
Attention! Пациентов необходимо предупредить о том, что им следует немедленно обратиться к врачу при появлении необъяснимых болей или мышечной слабости, особенно если они сопровождаются недомоганием или лихорадкой.
Препарат Аторвастатин содержит лактозу, в связи с чем его применение пациентами с дефицитом лактазы, непереносимостью лактозы и синдромом глюкозо-галактозной мальабсорбции противопоказано.
Effects on ability to drive vehicles and mechanisms
Следует соблюдать осторожность при управлении транспортными средствами и другими техническими устройствами, требующими повышенной концентрации внимания и быстроты психомоторных реакций (риск развития головокружения).
Storage conditions
Store in a dark place at a temperature not higher than 25 C.
Keep out of the reach of children.
Dosing and Administration
Inside. Taken at any time of the day regardless of the meal.
Перед началом лечения препаратом Аторвастатин следует попытаться добиться контроля гиперхолестеринемии с помощью диеты, физических упражнений и снижения массы тела у пациентов с ожирением, а также лечением основного заболевания.
При назначении препарата пациенту необходимо рекомендовать стандартную гипохолестеринемическую диету, которой он должен придерживаться в течение всего периода лечения.
Доза препарата варьирует от 10 мг до 80 мг 1 раз в сутки и титруется с учетом исходной концентрации Хс-ЛПНП, цели терапии и индивидуального эффекта на проводимую терапию.
The maximum daily dose is 80 mg.
В начале лечения и/или во время повышения дозы препарата Аторвастатин необходимо каждые 2-4 недели контролировать концентрацию липидов в плазме крови и соответствующим образом корректировать дозу.
Первичная гиперхолестеринемия и комбинированная (смешанная) гиперлипидемия
Лечение начинают с рекомендуемой начальной дозы 10 мг 1 раз в сутки, которую увеличивают после четырех недель в зависимости от реакции пациента. The maximum daily dose is 80 mg.
Гомозиготная семейная гиперхолестеринемия
The dose range is the same as for other types of hyperlipidemia. The initial dose is selected individually depending on the disease severity. У большинства пациентов с гомозиготной наследственной гиперхолестеринемией оптимальный эффект наблюдается при применении препарата в суточной дозе 80 мг (однократно). Аторвастатин применяется в качестве дополнительной терапии к другим методам лечения (плазмаферез) или как основное лечение, если терапия с помощью других методов невозможна.
У пациентов с нарушениями функции печени необходима осторожность (в связи с замедлением выведения аторвастатина из организма). В подобной ситуации следует тщательно контролировать клинические и лабораторные показатели (регулярный контроль активности аспартатаминотрансферазы (ACT) и аланинаминотрансферазы (АЛТ)). При значительном повышении активности «печеночных» трансаминаз доза препарата должна быть уменьшена или лечение должно быть прекращено.
У пациентов пожилого возраста и у пациентов с заболеваниями почек дозу препарата изменять не следует. Нарушение функции почек не оказывает влияния на концентрацию аторвастатина в плазме крови или степень снижения концентрации Хс-ЛПНП при терапии аторвастатином, поэтому коррекции дозы препарата не требуется.
Применение в комбинации с другими лекарственными средствами
При необходимости одновременного применения с циклоспорином, телапревиром или комбинацией типрапавир/ритонавир доза препарата не должна превышать 10 мг в сутки.
Следует соблюдать осторожность и применять самую низкую эффективную дозу аторвастатина при одновременном применении с ингибиторами протеазы ВИЧ, ингибиторами гепатита С, кларитромицином и итраконазолом.
Рекомендации для определения цели лечения
Рекомендации Европейского общества атеросклероза
У пациентов с подтвержденным диагнозом ИБС и других пациентов с высоким риском ишемических осложнений целью лечения является снижение концентрации Хс-ЛПНП до концентрации ниже 2,5 ммоль/л (или менее 100 мг/дл) и общего холестерина до концентрации ниже 4,5 ммоль/л (или менее 175 мг/дл).
Information
Appearance may differ from that depicted in the picture. There are contraindications. You need to read the manual or consult with a specialist