Novostat - instructions for use, doses, side effects, contraindications

Excipients: lactose monohydrate (sugar milk) - 98.26 mg, microcrystalline cellulose - 30.0 mg, sodium lauryl sulfate - 1.0 mg, povidone - K17 - 5.0 mg, calcium carbonate - 35.0 mg, sodium carboxymethyl starch - 8, 0 mg, magnesium stearate 1.9 mg.

Capsule composition:

Housing: titanium dioxide - 2.0%, gelatin - up to 100%.

Cap: iron oxide oxide yellow - 0.1%, titanium dioxide 2.0%, gelatin - up to 100%.

Capsule 20.0 mg:

Active substance: atorvastatin calcium trihydrate (crystalline) 21.69 mg, calculated as atorvastatin 20.0 mg.

Excipients: lactose monohydrate (milk sugar) 87.41 mg, microcrystalline cellulose 30.0 mg, sodium lauryl sulfate 1.0 mg, povidone K17 5.0 mg, calcium carbonate 35.0 mg, sodium carboxymethyl starch 8, 0 mg, magnesium stearate 1.9 mg.

Capsule composition:

Housing: iron oxide oxide yellow - 0.1%, titanium dioxide 2.0%, gelatin - up to 100%.

Cap: iron oxide oxide yellow - 0.1%, titanium dioxide 2.0%, gelatin - up to 100%.

Capsule 40.0 mg:

Active substance: atorvastatin calcium trihydrate (crystalline) 43.37 mg, calculated as atorvastatin 40.0 mg.

Excipients: lactose monohydrate (milk sugar) - 174.83 mg, microcrystalline cellulose - 60.0 mg, sodium lauryl sulfate - 2.0 mg, povidone - K17 - 10.0 mg, calcium carbonate - 70.0 mg, sodium carboxymethyl starch - 16 , 0 mg, magnesium stearate - 3.8 mg.

Capsule composition:

Housing: iron oxide oxide yellow - 0.1763%, titanium dioxide - 0.9744%, gelatin - up to 100%.

Cap: iron oxide oxide yellow - 0.1763%, titanium dioxide - 0.9744%, gelatin - up to 100%.

Capsule 80.0 mg:

Active substance: atorvastatin calcium trihydrate (crystalline) 86.74 mg, calculated as atorvastatin 80.0 mg.

Excipientslactose monohydrate (sugar milk) - 131.46 mg, microcrystalline cellulose - 60.0 mg, sodium lauryl sulfate - 2.0 mg, povidone - K17 - 10.0 mg, calcium carbonate - 70.0 mg, sodium carboxymethyl starch - 16 , 0 mg, magnesium stearate - 3.8 mg.

Capsule composition:

Housing: iron dye oxide yellow 0.2%, ferric oxide black oxide 0.53%, iron oxide red oxide 0.93%, titanium dioxide 0.3333%, gelatin 100%.

Cap: dye iron oxide yellow - 0.2%, iron dye oxide black - 0.53 %, ferric oxide red oxide - 0.93%, titanium dioxide 0.3333%, gelatin - up to 100%.

Description:

Dosage of 10 mg. Capsules hard gelatinous № 2. The case of white color, a lid of yellow color with a light beige shade opaque.

Dosage of 20 mg. Capsules hard gelatinous № 2. The case and a cover of yellow color with light beige shade opaque.

The dosage is 40 mg. Capsules hard gelatinous № 0. The case and a cover of light yellow color with a beige shade opaque.

Dosage of 80 mg. Capsules hard gelatinous № 0. The case and a cover of dark brown color opaque.

The contents of the capsules are a mixture of powder and granules of white or almost white color. It is allowed to compact the contents of the capsules into lumps in the form of capsules, which is easily destroyed when pressed.

Pharmacotherapeutic group:Hypolipidemic agent - inhibitor of HMG-CoA reductase

ATX: & nbsp

C.10.A.A Inhibitors of HMG-CoA reductase

C.10.A.A.05 Atorvastatin

Pharmacodynamics:

Synthetic lipid-lowering agent. Atorvastatin - a selective competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A-reductase (HMG-CoA reductase), a key enzyme that converts 3-hydroxy-3-methylglutaryl-CoA into the mevalonate precursor of sterols, including cholesterol.

In patients with homozygous and heterozygous familial hypercholesterolemia, non-family forms of hypercholesterolemia and mixed dyslipidemia atorvastatin reduces the concentration in the blood plasma of total cholesterol (cholesterol), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (Apo-B), and very low-density lipoprotein cholesterol (cholesterol-VLDL) and triglycerides (TG), causes an unstable increase concentration of high-density lipoprotein cholesterol (HDL-C).

Atorvastatin lowers the concentration of cholesterol and lipoproteins in the blood plasma, inhibiting HMG-CoA reductase and the synthesis of cholesterol in the liver and increasing the number of "liver" LDL receptors on the cell surface, which leads to an increase in the capture and catabolism of LDL-C.

Atorvastatin reduces the formation of LDL-C and the number of LDL particles, causes a marked and persistent increase in the activity of LDL receptors in combination with favorable qualitative changes in LDL-particles, and also reduces the concentration of LDL-C in patients with homozygous hereditary familial hypercholesterolemia, resistant to therapy with other lipid-lowering means.

Atorvastatin in doses from 10 mg to 80 mg reduces the concentration of total cholesterol by 30-46%, LDL-cholesterol by 41-61%, Apo-B by 34-50% and TG by 14-33%. The results of therapy are similar 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, HDL-VLD, Apo-B and TG and increases the concentration of cholesterol-HDL.In patients with disbetalipoproteinemia atorvastatin reduces the concentration of intermediate-density lipoprotein cholesterol. In patients with hyperlipoproteinemia of the type IIa and IIb According to Fredrickson, the average increase in the concentration of cholesterol-HDL in the treatment with atorvastatin (10-80 mg) compared with the initial index is 5.1-8.7% and is dose-independent. There is a significant dose-dependent reduction in the ratio: total cholesterol / HDL-C and LDL-C-HDL-C cholesterol by 29-44% and 37-55%, respectively.

Atorvastatin 80 mg significantly reduces the risk of ischemic complications and mortality by 16% after a 16-week course, and the risk of re-hospitalization for angina pectoris accompanied by signs of myocardial ischemia is 26%. In patients with different baseline concentrations of LDL-C atorvastatin causes a reduction in the risk of ischemic complications and mortality (in patients with myocardial infarction without a tooth Q and unstable angina, as well as in men and women, and in patients younger than 65 years of age). Reducing the concentration in the blood plasma of LDL-C is better correlated with the dose of the drug than with its concentration in the blood plasma. The dose is selected taking into account the therapeutic effect (see section "Method of administration and dose").The therapeutic effect is achieved 2 weeks after the initiation of therapy, reaches a maximum after 4 weeks, and persists throughout the period of therapy.

Atorvastatin 10 mg reduces the fatal and nonfatal outcomes of coronary heart disease (CHD) compared with placebo in patients with hypertension with three or more risk factors.

Pharmacokinetics:

Suction

Atorvastatin is rapidly absorbed after oral administration: the time to reach it maximum concentration (TC_m_Oh) in blood plasma - 1-2 hours In women, the maximum concentration of atorvastatin (C_m_Oh) by 20 % above, and the area under the curve "concentration-time" (AUC) - 10% lower than that of men. The degree of absorption and concentration in the blood plasma increase in proportion to the dose. Absolute bioavailability is about 14%, and systemic bioavailability of inhibitory activity against HMG-CoA reductase is about 30%. Low systemic bioavailability due to pre-systemic metabolism in the mucosa of the gastrointestinal tract and / or in the "primary passage" through the liver. Eating somewhat reduces the speed and degree of absorption of the drug (by 25% and 9% %, respectively, as evidenced by the results of the determination of C_m_Oh and AUC), however, a decrease in LDL-C is similar to that of fasting atorvastatin. Despite the fact that after taking atorvastatin in the evening, its concentration in the blood plasma is lower (C_m_Oh and AUC, approximately 30%) than after taking in the morning, the decrease in the concentration of LDL-C is not dependent on the time of day in which the drug is taken.

Distribution

The average volume of atorvastatin distribution is about 381 liters. The connection with plasma proteins is not less than 98%. The ratio of the erythrocyte / plasma content is about 0.25, i.e. atorvastatin poorly penetrates into red blood cells.

Metabolism

Atorvastatin is largely metabolized with the formation of ortho- and para-hydroxylated derivatives and various products (3-oxidation. In vitro ortho- and para-hydroxylated metabolites have an inhibitory effect on HMG-CoA reductase, comparable to that of atorvastatin. Approximately 70% decrease in the activity of HMG-CoA reductase occurs due to the action of active circulating metabolites. Research results in vitro suggest that isoenzyme CYP3A4 The liver plays an important role in the metabolism of atorvastatin.In favor of this fact is an increase in the concentration of atorvastatin in blood plasma with the simultaneous administration of erythromycin, which is an inhibitor of this isoenzyme. Research in vitro They also showed that atorvastatin is a weak isoenzyme inhibitor CYP3A4. Atorvastatin does not have a clinically significant effect on the concentration in the blood plasma of terfenadine, which is metabolized mainly by isoenzyme CYP3A4, therefore, its significant effect on the pharmacokinetics of other isoenzyme substrates CYP3A4 is unlikely (see the section "Interaction with other drugs").

Excretion

Atorvastatin and its metabolites are excreted mainly through the intestines with bile after hepatic and / or extrahepatic metabolism (atorvastatin not subject to severe intestinal hepatic recirculation). The half-life period (T1 / 2) is about 14 hours, while the inhibitory effect of the drug against HMG-CoA reductase is approximately 70% determined by the activity of circulating metabolites and remains about 20-30 hours due to their presence. After ingestion, in urine is detected less than 2% of the accepted dose of the drug.

Special patient groups

Elderly patients

The concentrations of atorvastatin in the blood plasma of patients older than 65 years are higher (C_m_Ohby about 40%, AUC approximately 30%) than in adult patients of a young age. Differences in the efficacy and safety of the drug, or the achievement of the goals of lipid-lowering therapy in elderly patients, as compared to the general population, have not been revealed.

Children

Studies of the pharmacokinetics of the drug in children have not been conducted.

Lack of kidney function

Disturbance of renal function does not affect the concentration of atorvastatin in the blood plasma or the effect on lipid metabolism, therefore, a dose change in patients with impaired renal function is not required (see the "Method of administration and dose" section) Atorvastatin is not excreted during hemodialysis due to intensive binding to blood plasma proteins.

Lack of liver function

The concentration of atorvastatin is significantly increased (C_m_Oh about 16 times, AUC approximately 11 times) in patients with alcoholic liver cirrhosis (class B according to the Child-Pugh classification) (see "Contraindications").

Indications:

- primary hypercholesterolemia (heterozygous familial and non-family hypercholesterolemia (type IIbut according to Fredrickson's classification);

- combined (mixed) hyperlipidemia (type IIa and IIb according to Fredrickson's classification);

- dysetalopoproteinemia (type III according to Fredrickson's classification) (as a supplement to the hypocholesterol diet);

- family endogenous hypertriglyceridemia (type IV according to Fredrickson classification), resistant to hypocholesterol diet;

- homozygous familial hypercholesterolemia with insufficient effectiveness of diet therapy and other non-pharmacological methods of treatment;

- primary prevention of cardiovascular complications in patients without clinical signs of coronary heart disease, but having several risk factors for its development: age over 55, nicotine dependence,

- Arterial hypertension, diabetes mellitus, low concentrations of cholesterol-HDL in the blood plasma, genetic predisposition, including against the background of dyslipidemia;
- secondary prevention of cardiovascular complications in patients with coronary heart disease in order to reduce the overall mortality rate, myocardial infarction,stroke, repeated hospitalization for angina pectoris and the need for revascularization procedures.

Contraindications:

- Hypersensitivity to any component of the drug.

- Active liver disease or increased activity of "hepatic" transaminases in blood plasma of unknown origin more than 3 times compared with the upper limit of the norm (VGN).

- Age to 18 years (not enough clinical data on the efficacy and safety of the drug in this age group).

- The use in women of reproductive age, not using adequate methods of contraception.

- Pregnancy, the period of breastfeeding.

- Lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

Carefully:Alcohol abuse, liver disease in history, severe water-electrolyte balance disorders, endocrine and metabolic disorders, arterial hypotension, severe acute infections (sepsis), uncontrolled epilepsy, extensive surgical interventions, injuries, skeletal muscle diseases, diabetes mellitus.

Pregnancy and lactation:Atorvastatin is contraindicated in pregnancy and during breastfeeding.

Women of reproductive age during treatment should use adequate means of contraception. Atorvastatin can be prescribed to women of reproductive age only if the probability of pregnancy is very low, and the patient is informed of the possible risk of treatment for the fetus. Because cholesterol and substances synthesized from cholesterol are important for the development of the fetus, the potential risk of inhibiting HMG-CoA reductase exceeds the use of atorvastatin during pregnancy. In the case of pregnancy diagnosis, the drug should be discontinued as soon as possible, and the patient is warned about the potential risk to the fetus.

It is not known whether atorvastatin with breast milk. Given the potential for adverse effects in infants, if necessary, use during lactation should decide the issue of termination of breastfeeding.

Dosing and Administration:

Inside. Take at any time of the day, regardless of food intake.Before starting treatment, the drug should try to achieve control of hypercholesterolemia with diet, exercise and weight loss in obese patients, as well as therapy for the underlying disease. When appointing the drug, the patient should recommend a standard hypocholesterolemic diet, which he must adhere to throughout the period of therapy.

The dose of the drug varies from 10 mg to 80 mg once a day and is titrated taking into account the initial content of LDL-C, the purpose of therapy and the individual effect on the therapy.

The maximum daily dose of the drug for a single dose is 80 mg.

At the beginning of treatment and / or during an increase in the dose of the drug, it is necessary to monitor the concentration of lipids in the blood plasma every 2-4 weeks and adjust the dose accordingly.

Primary hypercholesterolemia and combined (mixed) hyperlipidemia

For the majority of patients - 10 mg once a day; The therapeutic effect is manifested during 2 weeks of therapy and usually reaches a maximum within 4 weeks. With prolonged treatment, the effect persists.

Homozygous familial hypercholesterolemia

In most cases, appoint 80 mg once a day (reducing the concentration of LDL-C in 18-45%).

Lack of liver function

If liver function is insufficient, the dose of the drug should be reduced, with the regular monitoring of the activity of "liver" transaminases: aspartate aminotransferase (ACT) and alanine aminotransferase (ALT).

Lack of kidney function

The renal dysfunction does not affect the concentration of atorvastatin in the blood plasma or the degree of decrease in the concentration of LDL-C in the treatment with the drug, so dose adjustment is not required.

Elderly patients

Differences in the efficacy, safety or therapeutic effect of the drug in elderly patients are not found in comparison with the general population and no dose adjustment is required (see the section "Pharmacokinetics").

Use in combination with other medicines

If a simultaneous application with cyclosporine is required, the dose of the drug should not exceed 10 mg per day (see section "Special instructions")

Caution should be exercised and the lowest effective dose of atorvastatin should be used when used simultaneously with HIV protease inhibitors, hepatitis C inhibitors, clarithromycin and itraconazole.

Side effects:

The incidence of side effects is classified according to the recommendations of the World Health Organization: very often - not less than 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely (including individual messages) - less than 0.01%, frequency unknown - can not be calculated from available data.

On the part of the blood and lymphatic system: rarely - thrombocytopenia.

From the immune system: often - allergic reactions; rarely - angioedema; anaphylactic shock.

From the nervous system: often - headache; infrequently - dizziness, paresthesia, hypoesthesia, amnesia, a violation of taste, insomnia, "nightmarish" dreams; rarely - peripheral neuropathy; frequency unknown - Depression.

From the side of the organ of vision: infrequently - decreased vision clarity; rarely - impaired visual perception.

From the side of the hearing organ and labyrinthine disorders: infrequently - "noise in ears, rarely - loss of hearing.

On the part of the respiratory system, the organs of the thorax and the mediastinum: often - nasopharyngitis, epistaxis, pain in the pharyngeal region; frequency unknown - interstitial lung disease.

From the side of the digestive tract: often - Nausea, flatulence, constipation, indigestion, diarrhea; infrequently - belching, vomiting, abdominal pain, pancreatitis.

From the liver and biliary tract: infrequently - hepatitis; rarely - cholestasis; rarely - hepatic insufficiency, cholestatic jaundice.

From the skin and subcutaneous tissues: infrequently - Alopecia, skin rash, itching, hives; rarely - bullous dermatitis, erythema multiforme; rarely - Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).

From the musculoskeletal system and connective tissue: often - myalgia, arthralgia, pain in the limbs, muscle spasm, back pain, "swelling" of the joints; infrequently - pain in the neck, muscle weakness; rarely - myopathy, myositis, rhabdomyolysis, tendonopathy, complicated by a rupture of the tendon; frequency unknown - immuno-mediated necrotizing myopathy.

From the side of the reproductive system: rarely - gynecomastia; frequency unknown - impotence.

Common violations: infrequently - asthenia, weakness, chest pain, peripheral edema, fever, increased fatigue, weight gain, anorexia.

Laboratory indicators: often - hyperglycemia, increased activity kreatinfosfokinazy in the blood serum; infrequently - leukocyturia, hypoglycemia, increased activity of "liver" transaminases.

When using inhibitors of HMG-CoA reductase (statins), including atorvastatin, there were cases of increased glycosylated hemoglobin.

Overdose:

There is no specific antidote for overdose treatment with the drug.

In case of overdose, symptomatic treatment should be performed as needed. It is necessary to monitor the liver function and the activity of creatine phosphokinase (CK) in the blood serum. Since the drug actively binds to blood plasma proteins, hemodialysis is ineffective.

Interaction:

The risk of myopathy during treatment with HMG-CoA reductase inhibitors increases with simultaneous use of cyclosporine, fibrates, erythromycin, clarithromycin, antifungal agents - azole derivatives, - and nicotinic acid in lipid-lowering doses (see section "Special instructions").

Inhibitor inhibitors CYP3A4

Because the atorvastatin is metabolized by isoenzyme CYP3A4, simultaneous use of atorvastatin with isozyme inhibitors CYP3A4 can lead to an increase in the concentration of atorvastatin in the blood plasma. The degree of interaction and the effect of potentiation are determined by the variability of the effect on the isoenzyme CYP3A4. The simultaneous use of atorvastatin with drugs that reduce the concentration of endogenous steroid hormones (including cimetidine, ketoconazole, spironolactone) increases the risk of reducing endogenous steroid hormones.

Inhibitors of transport protein OATP1B1

Atorvastatin and its metabolites are substrates of the transport protein OATP1B1. Inhibitors of OATP1B1 (for example, ciclosporin) may increase the bioavailability of atorvastatin. Thus, simultaneous use of atorvastatin 10 mg and cyclosporine at a dose of 5.2 mg / kg / day leads to an increase in the concentration of atorvastatin in blood plasma by 7.7 times (see the section "Method of administration and dose").

Erythromycin / clarithromycin

With simultaneous use of atorvastatin and erythromycin (500 mg 4 times a day) or clarithromycin (500 mg twice a day), which inhibit the isoenzyme CYP3A4, an increase in the concentration of atorvastatin in the blood plasma was observed (see section "Special instructions").

HIV protease inhibitors

The simultaneous use of HIV protease inhibitors (fosamprenavir, nelfinavir, lopinavir / ritonavir, saquinavir / ritonavir, darunavir / ritonavir, fosamprenavir / ritonavir) with atorvastatin leads to an increase atorvastatin plasma concentration.

Hepatitis C protease inhibitors

Protease inhibitors of hepatitis C (boseprevir) while the application of atorvastatin, atorvastatin leads to an increase in concentration in the blood plasma.

Diltiazem

Simultaneous use of atorvastatin in a dose of 40 mg with diltiazem in a dose of 240 mg, leads to an increase in the concentration of atorvastatin in blood plasma.

Cimetidine

Clinically significant interaction of atorvastatin with cimetidine was not detected.

Itraconazole

The simultaneous use of atorvastatin in doses of 20 mg to 40 mg and itraconazole at a dose of 200 mg resulted in an increase in the value AUC atorvastatin.

Grapefruit juice

Because grapefruit juice contains one or more components that inhibit the isoenzyme CYP3A4, its excessive consumption (more than 1.2 liters per day) can cause an increase in the concentration of atorvastatin in the blood plasma.

Inductors of cytochrome isoenzyme CYP3A4

Combined use of atorvastatin with isoenzyme inducers CYP3A4 (eg, efavirenz, rifampicin, phenytoin) can lead to a decrease in the concentration of atorvastatin in the blood plasma. Due to the dual mechanism of interaction with rifampicin (isoenzyme inducer CYP3A4 and inhibitor of hepatocyte transport protein OATP1B1), simultaneous use of atorvastatin and rifampicin is recommended, since delayed administration of atorvastatin after taking rifampicin results in a significant decrease in the concentration of atorvastatin in blood plasma.

Antacids

Simultaneous ingestion of a suspension containing magnesium hydroxide and aluminum hydroxide reduced the concentration of atorvastatin in the blood plasma by approximately 35%, but the degree of decrease in the concentration of LDL-C was not changed.

Fenazone

Atorvastatin does not affect the pharmacokinetics of phenazone, therefore interaction with other drugs metabolized by the same isoenzymes of cytochrome is not expected.

Kolestypol

With the simultaneous use of colestipol, the concentration of atorvastatin in the blood plasma decreased by about 25%; however, hypolipidemicthe effect of a combination of atorvastatin and colestipol was superior to that of each drug alone.

Digoxin

With repeated administration of digoxin and atorvastatin at a dose of 10 mg, the equilibrium concentrations of digoxin in the blood plasma did not change. However, when using digoxin in combination with atorvastatin in a dose of 80 mg / day. the digoxin concentration increased by about 20%. Patients receiving digoxin in combination with atorvastatin, require appropriate monitoring.

Azithromycin

With the simultaneous use of atorvastatin at a dose of 10 mg 1 time per day and azithromycin at a dose of 500 mg per day, the concentration of atorvastatin in the blood plasma did not change.

Oral contraceptives

With simultaneous use of atorvastatin and oral contraceptive containing norethisterone and ethinyl estradiol, there was a significant increase AUC norethisterone and ethinyl estradiol by about 30% and 20%, respectively. This effect should be considered when choosing an oral contraceptive for a woman receiving atorvastatin.

Terfenadine

With the simultaneous use of atorvastatin and terfenadine, clinically significant changes in the pharmacokinetics of terfenadinerevealed.

Warfarin

There were no signs of a clinically significant interaction of atorvastatin with warfarin.

Amlodipine

With simultaneous use of atorvastatin in a dose of 80 mg and amlodipine at a dose of 10 mg, the pharmacokinetics of atorvastatin did not change in the equilibrium state.

Fusidic acid

With the simultaneous use of atorvastatin with fusidic acid, the risk of rhabdomyolysis increases. With their simultaneous use, the concentration of both fusidic acid and atorvastatin in the blood plasma can be increased. The mechanism of this interaction is still not known. If treatment with fusidic acid is necessary, treatment with atorvastatin should be discontinued.

Colchicine

Caution should be exercised with the simultaneous use of atorvastatin with colchicine, since cases of myopathy have been described.

Special instructions:

Before starting therapy with Novostat, the patient should be prescribed a standard hypocholesterol diet, which he must observe during the entire treatment period.

The use of HMG-CoA reductase inhibitors to reduce lipid levels in the blood can lead to a change in biochemical parameters that reflect the function of the liver.The liver function should be monitored before the start of therapy, 6 weeks, 12 weeks after the start of taking Novostat and after each dose increase, and periodically, for example, every 6 months. Increased activity of "liver" Enzymes in the blood serum can be observed during therapy with Novostat.

Patients who have an increase in enzyme activity should be monitored before the enzyme activity returns to normal. In the case of a persistent increase in ALT activity or ACT to a level exceeding more than 3 times the IGN, it is recommended to reduce the dose of Novostat or stop treatment.

Novostat should be used with caution in patients who abuse alcohol and / or have liver disease. Active liver disease or persistent increase in the activity of aminotransferases of unknown origin is a contraindication to the appointment of Novostat.

Treatment with Novostat, as well as with other inhibitors of HMG-CoA reductase, can cause myopathy. The diagnosis of myopathy (pain and weakness in muscles combined with an increase in CKK activity by more than 10 times compared to IGN) should be discussed in patients with advanced myalgia, tenderness or weakness of the muscles and / or a marked increase in CKK activity.Patients should be warned that they should immediately inform the doctor of unexplained pain or weakness in the muscles if they are accompanied by a malaise or fever. Novostat therapy should be discontinued in the event of a marked increase in CPK activity or in the presence of confirmed or suspected myopathy. The risk of myopathy in treatment with other drugs of this class increased with simultaneous use of cyclosporine, fibrates, erythromycin, nicotinic acid in lipid-lowering doses (more than 1 g / day) or azole antifungal agents. Many of these drugs inhibit cytochrome P4503A4-mediated metabolism and / or drug transport. Atorvastatin biotransformed by isoenzyme CYP AP4.

When appointing Novostat in combination with fibrates, erythromycin, immunosuppressive agents, azole antifungal agents or nicotinic acid in lipid-lowering doses (more than 1 g / day), the expected benefit and risk of treatment should be carefully weighed and patients monitored regularly to identify pain or weakness in the muscles, especially during the first months of treatment and during the period of increasing the dose of any drug.In such situations, it is possible to recommend a periodic determination of the activity of CKK, although such control does not prevent the development of severe myopathy.

When Novostat, as well as other agents of this class, describes cases of rhabdomyolysis with acute renal failure due to myoglobinuria. Novostat therapy should be temporarily discontinued or completely abolished if there is evidence of possible myopathy or the presence of a risk factor for developing renal disease insufficiency on the background of rhabdomyolysis (for example, severe acute infection, arterial hypotension, serious surgery, trauma, severe metabolic, endocrine and water-electrolyte disorders and uncontrolled convulsions).

Before starting therapy with Novostat, it is necessary to try to achieve control of hypercholesterolemia by adequate diet therapy, increasing physical activity, reducing body weight in obese patients and treating other conditions. Patients should be warned that they should immediately consult a doctor if unexplained pain or weakness in the muscles occurs, especially if they are accompanied by a malaise or fever.

When using inhibitors of HMG-CoA reductase (statins), including atorvastatin, there were cases of increased glycosylated hemoglobin and fasting plasma glucose concentration. However, the risk of hyperglycaemia is lower than the degree of reduction in the risk of vascular complications in patients receiving statins.

Effect on the ability to drive transp. cf. and fur:The adverse effect of atorvastatin on the ability to drive vehicles and engage in potential hazardous activities requiring increased concentration and speed of psychomotor reactions was not reported. However, given the possibility of developing dizziness, care should be taken when performing the listed activities.

Form release / dosage:

Capsules 10 mg, 20 mg, 40 mg and 80 mg.

Packaging:

10, 20, 30 capsules in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered. For 10, 20, 30, 40, 50, 60 or 100 capsules in cans of polymeric for medicines. One jar or 1, 2, 3, 4, 5, 6, 9 or 10 contour mesh packages together with the instruction for use are placed in a cardboard package (bundle).

It is allowed to bundle 2 or 3 cardboard packages (packs) into a group package (shipping container) from cardboard for consumer packaging.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years. Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002678

Date of registration:24.10.2014

The owner of the registration certificate:ATOLL, LLC ATOLL, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Information update date: & nbsp24.10.2014

Illustrated instructions

Instructions

Novostat (Novostat)