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

Excipients: mannitol - 68.38 mg; 136.76 mg or 273.52 mg, cellulose microcrystalline - 18.0 mg; 36.0 mg or 72.0 mg, crospovidone - 12.0 mg; 24.0 mg or 48.0 mg, sodium carbonate 6.6 mg; 13.2 mg or 26.4 mg, povidone 2.4 mg; 4.8 mg or 9.6 mg, magnesium stearate-1.92 mg; 3.84 mg or 7.68 mg;

tablet shell: Opaglos 2 white 97W18453 (aqueous solution 8:92) 3.6 mg; 7.2 mg or 14.4 mg: carmellose sodium (45%), maltodextrin (23%), dextrose monohydrate (19%), titanium dioxide (10%), stearic acid (3%).

Description:

Tablets 10 mg: oval, biconvex, coated with a film shell white tablets with engraving "10" on one side and "A" on the other side.

Tablets of 20 mg: oval, biconvex, coated with a film shell white tablets with engraving "20" on one side and "A" on the other side.

Tablets 40 mg: oval biconvex, coated with a film shell white tablets with engraving "40" on one side and "A" on the other side.

In the fracture, the core is white or almost white, covered with a continuous coat of white color.

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:

Hypolipidemic agent from the group of HMG-CoA reductase inhibitors (statins). A selective competitive inhibitor of HMG-CoA reductase, an enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A into mevalonic acid, a precursor of sterols, including cholesterol. Triglycerides (TG) and cholesterol in liver are included in the composition of very low density lipoproteins (VLDL), enter the blood plasma and transport to peripheral tissues. Low density lipoproteins (LDL) are formed from VLDL in the course of interaction with LDL receptors. Atorvastatin reduces the concentration of cholesterol and lipoproteins in the blood plasma by inhibiting HMG-CoA reductase, the synthesis of cholesterol in the liver and increasing the number of "liver" LDL receptors on the cell surface, which leads to an increase seizure and catabolism of LDL. Reduces the formation of LDL, causes a pronounced and persistent increase in the activity of LDL receptors. Dose-dependent decreases the concentration of LDL in patients with homozygous familial hypercholesterolemia, which usually does not respond to therapy lipid-lowering drugs. Reduces the concentration of total cholesterol (Xs) by 30-46%, LDL - by 41-61%, apolipoproteinIn (apo-B) - by 34-50% and TG - by 14-33%, causes an increase in the concentration of high-density lipoprotein cholesterol (Xc-HDL) and apolipoprotein A.

The results of treatment are similar in patients with heterozygous familial hypercholesterolemia, non-family forms of hypercholesterolemia and mixed hyperlipidemia,in t.ch. in patients with type 2 diabetes mellitus.

In patients with isolated hypertriglyceridemia atorvastatin reduces the concentration of Xc, low-density lipoprotein cholesterol (Xc-LDL), very low density lipoprotein cholesterol (Xc-VLDL), apo-B and TG; causes an unstable increase in the concentration of HDL-C. In patients with disbetalipoproteinemia, the concentration of intermediate-density lipoprotein cholesterol (Xc-LLTP) is reduced.

In patients with hyperlipoproteinemia of the type IIa and IIb according to Fredrickson classification, the average value of increasing the concentration of X-HDL in the treatment with atorvastatin (10 - 80 mg), compared with the initial index is 5.1-8.7% and dose-independent. There is a significant dose-dependent decrease in the ratio of Xc / Xc-HDL and Xc-LDL / Xc-HDL-C 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 reduces the risk of ischemic complications and mortality patients with myocardial infarction without a tooth Q and unstable angina, men and women, patients under the age of 65 years and older).

Reduced plasma levels of Xc-LDL are 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.

Pharmacokinetics:

Atorvastatin is rapidly absorbed after oral administration. The maximum concentration (Cmah) in the blood plasma is achieved after 1-2 hours, C_m_Oh in women higher by 20%, the area under the curve "concentration - time" (AUC) - lower by 10% compared to men. These differences are clinically insignificant, differences in the decrease in LDL-C in men and women are insignificant. The degree of absorption increases in proportion to the dose of atorvastatin taken.

Absolute bioavailability is about 14%, systemic bioavailability of inhibitory activity against HMG-CoA reductase is about 30%.Low systemic bioavailability is due to presystemic metabolism in the mucosa of the gastrointestinal tract and / or during primary passage through the liver.

The ratio of concentrations of atorvastatin in erythrocytes / plasma is about 0.25, i.e. atorvastatin poorly penetrates into red blood cells.

The degree of absorption and concentration of atorvastatin in the blood plasma increases in proportion to the dose. The intake of food reduces the rate and degree of absorption by approximately 25% and 9%, respectively (as indicated by the results of the determination of C_m_Oh and AUC), However, the concentration of Xc-LDL with the use of atorvastatin on an empty stomach and during meals decreases almost to the same extent. Despite the fact that after the use of atorvastatin in the evening, its concentration in the blood plasma is lower (Cmah and AUC approximately 30%) than after taking in the morning, the decrease in X-LDL does not depend on the time of day in which the drug is taken.

The average volume of distribution is about 381 liters, the connection with plasma proteins is 98%. Metabolized mainly in the liver under the action of cytochrome isoenzymes CYP3A4 with the formation of pharmacologically active metabolites (ortho- and para-hydroxylated derivatives, beta-oxidation products).In addition, these metabolites are subjected to glucuronation in addition to other biotransformation pathways. In vitro ortho- and para-hydroxylated metabolites have an inhibitory effect on HMG-CoA reductase, comparable to that of atorvastatin.

The inhibitory effect of atorvastatin against HMG-CoA reductase is approximately 70% determined by the activity of circulating metabolites and lasts about 20-30 hours due to their presence.

It is excreted through the intestine with bile after hepatic and / or extrahepatic metabolism (it does not undergo significant intestinal hepatic recirculation).

The half-life is about 14 hours. After ingestion, less than 2% of the dose of atorvastatin is detected in the urine.

Special patient groups

Patients over 65 years of age: The concentration of atorvastatin and its active metabolites in blood plasma was higher in healthy volunteers over 65 years of age (C_m_Oh by about 40%, AUC about 30%) compared with young patients, but differences inefficacy and safety of the drug or the achievement of the goals of lipid-lowering therapy in these age groups was not found.

Impaired renal function: do not affect the concentration of atorvastatin and its active metabolites in the blood plasma, as well as the lipid-lowering effect of the drugs.

Atorvastatin is not excreted during hemodialysis due to intensive binding to blood plasma proteins. In this regard, dose changes in patients with impaired renal function are not required.

Dysfunction of the liver: The concentration of atorvastatin and its active metabolites is significantly increased (C_m_Oh about 16 times, AUC - 11 times higher than normal) in patients with alcoholic cirrhosis of the liver (class B on the Child-Pugh scale).

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

Indications:

Hypercholesterolemia:

- in combination with a diet to reduce elevated concentrations of total cholesterol, LDL cholesterol, apolipoprotein B and triglyceride levels and increase HDL cholesterol levels in patients with primary hypercholesterolemia, heterozygous familial and non-familial hypercholesterolemia and combined (mixed) hyperlipidemia (types IIa and IIb by Fredrickson), when diet therapy and other non-pharmacological treatments are not effective enough;

- in conjunction with a diet for treating patients with elevated serum triglyceride concentrations (type IV according to Fredrickson) and patients with disbetalipoproteinemiey (Type III according to Fredrickson) whose diet therapy does not give adequate effect;

- to reduce the concentration of total cholesterol and LDL cholesterol in patients with homozygous familial hypercholesterolemia in combination with other types of therapy aimed at reducing the concentration of lipids (for example, LDL apheresis), or in the case when these types of treatment are not effective enough.

Primary prevention of cardiovascular complications in patients without clinical signs of coronary heart disease (CHD), but having several risk factors for its development - age over 55, nicotine dependence, arterial hypertension, diabetes mellitus, low concentrations of HDL cholesterol in blood plasma, genetic predisposition, incl. against the background of dyslipidemia.

As an additional "therapy (secondary prevention) in the presence of other risk factors in patients with ischemic heart disease in order to reduce the total mortality of myocardial infarction, stroke, re-hospitalization for angina and the need for revascularization.

Contraindications:

- increased sensitivity to the active component or to some auxiliary substance of the preparation;

- Glucose-galactose malabsorption (contains in the dextrose monohydrate);

- active liver disease or increased activity of "hepatic" enzymes of unknown origin (more than 3 times compared with the upper limit of the norm);

- myopathy;

- pregnancy;

- lactation period;

- children's age till 18 years.

Carefully:

Abuse of alcohol, liver disease in history, pronounced violations of the water-electrolyte balance.

Pregnancy and lactation:

Atorvastatin is contraindicated for use during pregnancy and lactation (breastfeeding).

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. Women of reproductive age during treatment should use adequate methods of contraception. Atorvastatin can be used in women of reproductive age only if the probability of pregnancy is very low, and the patient is informed of the possible risk to the fetus.

Dosing and Administration:

Before starting treatment should try to achieve control of hypercholesterolemia with using diet, exercise and weight loss in patients with obesity, as well as treatment of the underlying disease.

When applying drug the patient should be advised to standard hypocholesterolemic diet, which he must comply during the entire course treatment.

The drug is taken orally at any time of the day, regardless of the time of ingestion. The dose ranges from 10 mg to 1 80 mg once a day, dose selection should be made considering the initial concentrations of LDL-C, the goals of therapy and individual effect. The maximum dose is 80 mg once a day.

At the beginning of the treatment and / or during increasing doses of atorvastatin is necessary every 2-4 weeks to monitor the concentration of lipids in blood plasma and adjust the dose.

When primary hypercholesterolemia and combined (mixed) hyperlipidemia For most patients, the dose of atorvastatin is 10 mg once a day. The therapeutic effect develops within 2 weeks and usually reaches a maximum within 4 weeks. With prolonged treatment, the effect persists.

When heterozygous familial hypercholesterolemia the initial dose is 10 mg per day. The dose should be set individually for each patient and titrated for 4 weeks to a daily dose of 40 mg. Then the dose can be increased to 80 mg per day or take Atorvastatin in a dose of 40 mg once a day in combination with bile acid sequestrants.

When homozygous familial hypercholesterolemia the drug is prescribed in a dose of 10 to 80 mg once a day.

When primary and secondary prevention of cardiovascular diseases the initial dose is 10 mg per day. To achieve the target values of Xc-LDL, a higher dose of the drug may be required. The maximum daily dose of the drug is not should exceed 80 mg per day.

Recommendations for determining treatment goals

A. Recommendations of the US National Cholesterol Education Program

Risk Category	The target content of Xc-LDL (mg / dl)	The content of Xc-LDL, in which it is recommended lifestyle change (mg / dl)	The content of Xc-LDL, in which recommended pharmacotherapy (mg / dL)
CHD or risk of developing coronary artery disease (10-year risk> 20%)	<100	>100	>130 (100-129: possible pharmacotherapy)¹
More than 2 risk factors (10-year risk <20%)	<130	>130	10-year risk of 10% -20%:> 130 10-year-old risk <10%: >160
0-1 risk factor²	<160	>160	>190 (160-189: prescribe a drug that reduces the content of LDL-C)

¹Some experts recommend the use of lipid-lowering drugs that reduce the content of LDL-C, if lifestyle changes do not reduce its content to <100 mg / dL. Others prefer drugs that have a predominant effect on TG and LDL-C, such as a nicotinic acid and fibrates. The doctor may also postpone the pharmacotherapy in this subgroup.

²In the absence of risk factors or the presence of only one risk factor, almost all people have a 10-year risk of <10%, so its assessment is not required.

If the target LDL-C content is reached and the TG content is> 200 mg / dL, the secondary goal of the therapy is to lower the cholesterol content, excluding the HDL-C (total cholesterol-HDL-C), to a level higher than the target LDL-C 30 mg / dl in each risk category.

B. Recommendations of the European Society of Atherosclerosis

In patients with a confirmed diagnosis of coronary heart disease and in patients with a high risk of ischemic complications, the goal of therapyis to lower the LDL-C-cholesterol level to below 3 mmol / L (or less than 115 mg / dL) and total cholesterol to below 5 mmol / L (or less than 190 mg / dl).

With hepatic insufficiency The dose of atorvastatin should be reduced by monitoring the function of the liver.

Impaired renal function does not affect the concentration of atorvastatin in the blood plasma or the degree of decrease in the concentration of LDL-C during application of Atorvastatin, therefore, correction of the dose of the drug is not required.

When the drug is used in patients old age correction of the dose is not required.

If it is necessary to use the dose of the drug together with cyclosporine Atorvastatin should not exceed 10 mg per day.

Side effects:

The frequency of adverse reactions listed below was distributed as follows: often (> 1/100, <1/10), infrequently (> 1/1000, <1/100), rarely (> 1/10000, <1/1000); very rarely (<1/10000).

From the blood and lymphatic system: rarely - thrombocytopenia.

From the immune system: often - allergic reactions; very rarely anaphylaxis.

From the side of metabolism and nutrition: often - hyperglycemia; infrequently - hypoglycemia, weight gain, anorexia.

Disorders of the psyche: infrequently - "nightmarish" dreams, insomnia.

From the side of the nervous system: often headache; infrequently - dizziness, paresthesia, hypoesthesia, a violation of taste perception, amnesia; rarely peripheral neuropathy.

From the side of the organ of vision: infrequent - reduced vision; rarely the violation of visual perception.

From the side of the organ of hearing and labyrinthine disorders: infrequent - ringing in the ears; very rarely - hearing loss.

On the part of the respiratory system, chest and mediastinum: often-pharyngolaryngeal pain, epistaxis, nasopharyngitis.

From the gastrointestinal tract: often - constipation, flatulence, dyspepsia, nausea, diarrhea; infrequent - vomiting, pain in the epigastric and lower abdominal area, belching, pancreatitis.

From the liver and biliary tract: infrequently - hepatitis; rarely - cholestasis; very rarely liver failure.

From the skin and subcutaneous fat: rarely - hives, skin rashes, skin itching, alopecia; rarely angioedema, bullous dermatitis, including erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome).

From the osteomuscular and connective tissue: often - myalgia, arthralgia, pain in the extremities, muscle spasm, swelling of the joints, back pain; rarely in the neck, muscular fatigue; rarely - myopathy, myositis, rhabdomyolysis, tendopathy, sometimes accompanied by ruptures.

From the genitals and mammary glands: very rarely - gynecomastia.

General disorders and disorders at the injection site: infrequently - weakness, asthenia, chest pain, peripheral edema, fatigue, fever.

Laboratory and instrumental data: often - increased activity of creatine phosphokinase (CK), increased activity of "liver" transaminases, "infrequently - leukocyturia.

The following side effects were observed in the treatment with some statins:

- Sexual dysfunction (decreased potency)

- Depression

- Single cases of interstitial lung disease, especially with prolonged treatment

Diabetes mellitus: the frequency of appearance depends on the presence of risk factors (fasting glucose concentration> 5.6 mmol / L, body mass index> 30 kg / m2, elevated triglyceride concentration, arterial hypertension in the medical history).

Overdose:

Treatment: there is no specific antidote, symptomatic therapy is performed. It requires careful monitoring of liver function and activity of CK in serum.

Hemodialysis is ineffective, since atorvastatin largely binds to blood plasma proteins.

Interaction:

The risk of myopathy during treatment with other drugs of this class increases with simultaneous use of cyclosporine, fibrates, antibiotics of the macrolide group, including erythromycin, antifungal agents related to azoles, HIV protease inhibitors and nicotinic acid in lipid lowering doses (more than 1 g per day ). The combined use of these drugs can also lead to the development of rhabdomyolysis and renal insufficiency caused by myoglobinuria. Care should be taken to evaluate the expected benefits of using a combination of these drugs and the possible adverse effects on the patient.

With the simultaneous use of drugs that increase the concentration of atorvastatin in blood plasma, the minimum initial dose of the latter should be taken. During the combined use of cyclosporine,clarithromycin or itraconazole is recommended to take a minimum dose of atorvastatin and establish a thorough monitoring of this group of patients.

Inhibitors of cytochrome P4503A4

Atorvastatin is metabolized by cytochrome P4503A4. Interactions may occur with the simultaneous use of atorvastatin and cytochrome P4503A4 inhibitors (such as ciclosporin; antibiotics of the macrolide group, including erythromycin; nefazodone; antifungal agents related to azoles, including itraconazole and HIV protease inhibitors). Care is needed during the simultaneous use of atorvastatin and drugs of this group, as this may cause an increase in the concentration of atorvastatin in the blood plasma.

Inhibitors of transport protein OATP1B1

Atorvastatin and its metabolites are a substrate of OATP1B1 transport proteins. The combined use of atorvastatin 10 mg and cyclosporine 5.2 mg / kg / day leads to an increase in the concentration of atorvastatin in blood plasma by 7.7 times. If you need a joint application with cyclosporine, the dose of Atorvastatin should not exceed 10 mg.

Erythromycin, clarithromycin

At simultaneous the use of atorvastatin 80 mg once a day and erythromycin (500 mg 4 times / day), the total activity of atorvastatin is increased by 33%. With the simultaneous use of atorvastatin at a dose of 10 mg per day and clarithromycin (500 mg 2 times / day), there was an increase in the concentration of atorvastatin in the blood plasma by 3.4 times. With the simultaneous administration of clarithromycin with atorvastatin, a minimum dose of atorvastatin is recommended. At a dose above 40 mg, careful monitoring of the patient in a hospital setting is recommended.

Itraconazole

The combined use of atorvastatin 40 mg and itraconazole 200 mg per day leads to an increase in the concentration of atorvastatin in blood plasma in 2.5-3.3 times. If the use of these two drugs is necessary simultaneously, the maintenance dose of atorvastatin should not exceed 40 mg per day. When taking a daily dose of atorvastatin 80 mg, if itraconazole is started, it should be reduced. When, when dose reduction is not possible, atorvastatin (for short courses of antifungal therapy) can be temporarily discontinued.

Inhibitors of proteases

The combined use of atorvastatin and protease inhibitors that inhibit cytochrome P450 AP4 results in an increase in the concentration of atorvastatin in blood plasma by a factor of two.

It is necessary to monitor the concentration of lipids in the blood plasma in order to determine the lowest effective dose of atorvastatin.

Diltiazem

Simultaneous use of atorvastatin in a dose of 40 mg and diltiazem 240 mg increases the concentration of atorvastatin in blood plasma by 51%. After the beginning of diltiazem application and after titration of the dose, careful monitoring of the patient in a hospital environment is required.

Grapefruit juice

Grapefruit juice contains one or more inhibitors of cytochrome P450 3A4, its administration can cause an increase in the concentration in the blood plasma of drugs metabolized by cytochrome P450 ZA4. After consuming 1 cup of grapefruit juice (240 ml) AUC Atorvastatin increases by 37% and AUC of the active orthohydroxy metabolite is reduced by 20.4%. A large amount of grapefruit juice (more than 1.2 liters per day for 5 days) causes an increase AUC atorvastatin 2.5 times and AUC atorvastatin and its metabolites in 1,3 times. It is not recommended to drink grapefruit juice in large quantities with atorvastatin therapy.

Inductors of cytochrome P450 ZA4

Simultaneous use of atorvastatin and cytochrome P450 inductors ZA4 (for example, efavirenz, rifampicin or herbal preparations based on St. John's Wortperforated) can lead to a decrease in the concentration of atorvastatin in the blood plasma. Because of the double mechanism of action of rifampicin (induction of cytochrome P450 and the blocking of transport protein OATP1B1 in hepatocytes), its simultaneous use with atorvastatin is recommended, since delayed administration of atorvastatin after taking rifampicin results in a significant decrease in the concentration of atorvastatin in the blood plasma.

Fusidic acid

Studies of the interaction of atorvastatin and fusidic acid have not been conducted. With the joint intake of drugs from the group of inhibitors of HMG-CoA reductase (statins) and fusidic acid, there have been reports of the development of adverse reactions from the muscular system, including rhabdomyolysis. The mechanism of this interaction is not known. It should be carefully monitored by patients taking both atorvastatin and fuzidovuyu, including may require a temporary discontinuation of atorvastatin.

Joint use of other drugs

Digoxin

With the repeated use 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 at a dose of 80 mg per day, the digoxin concentration increased by about 20%. This interaction is due to the inhibition of P-glycoprotein (transport membrane protein). Careful monitoring of patients receiving digoxin in combination with atorvastatin.

Oral contraceptives

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

Kolestypol

With the simultaneous use of colestipol, concentrations of atorvastatin and its active metabolites in blood plasma decreased by approximately 25%. butThe hypolipidemic effect of the combination of atorvastatin and colestipol was superior to that of each drug alone.

Antacids

When combined with atorvastatin and a suspension containing magnesium hydroxide and aluminum hydroxide, the concentrations of atorvastatin in the blood plasma were reduced by approximately 35%, however, the extent, cholesterol / LDL cholesterol reduction This has not changed.

Clinically significant interaction of atorvastatin with warfarin not detected.

Phenazone and cimetidine

When studying the interaction of atorvastatin with warfarin and cimetidine, no clinically significant interaction was found.

Amlodipine

With the 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.

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 once a day, the concentration of atorvastatin in the blood plasma did not change.

Terfenadine

Atorvastatin with simultaneous application with terfenadine did not have a clinically significant effect on its pharmacokinetics.

Special instructions:

Before starting therapy with atorvastatin, the patient should be prescribed a standard hypocholesterolemic 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 therapy, 6 weeks, 12 weeks after the start of Atorvastatin and after each increase the dose, and periodically, for example, every 6 months. An increase in the activity of "hepatic" enzymes in the serum can be observed during therapy with Atorvastatin.

Patients who have an increase in enzyme activity should be monitored before the enzyme activity returns to normal. In the event that the values of ALT or ACT more than 3 times the upper limit of the norm, it is recommended to reduce the dose of atorvastatin or stop treatment (seesection Contraindications).

Atorvastatin should be used with caution in patients who abuse alcohol and / or having liver disease. Active liver disease or persistent increase in the activity of "liver" transaminases unclear genesis serve as a contraindication to the use of atorvastatin.

Treatment with atorvastatin may cause myopathy.The diagnosis of myopathy (pain and weakness in muscles combined with an increase in CKK activity of more than 10 times compared with the upper limit of normal) should be discussed in patients with common 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.

Therapy with Atorvastatin should be discontinued in the event of a marked increase in CPK activity or in the presence of confirmed or suspected myopathy (see section Contraindications). The risk of myopathy when treated with other drugs of this class is increased with the simultaneous use of cyclosporine, fibrates, erythromycin, nicotinic acid in lipid-lowering doses (more than 1 g / day) or antifungal agents - azole derivatives. Many of these drugs inhibit metabolism mediated by cytochrome P450 ZA4, and / or transport of drugs. Atorvastatin biotransformed by isoenzyme CYP AP4. Applying Atorvastatin In combination with fibrates, erythromycin, immunosuppressive agents, antifungal agents, azole derivatives, 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 treatment and during periods 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 using Atorvastatin, as well as other drugs of this class, cases of rhabdomyolysis with acute renal failure due to myoglobinuria are described. Therapy Atorvastatin should be temporarily discontinued or completely eliminated if there is evidence of possible myopathy or the presence of a risk factor for the development of renal insufficiency on the background of rhabdomyolysis (for example, severe acute infection, arterial hypotension, serious surgery, trauma, severe metabolic endocrine and electrolyte disorders and uncontrolled convulsions).

Before starting therapy with atorvastatin, you should try to achieve control of hypercholesterolemia by adequate diet therapy, increased physical activity, weight loss in patients with obesity.

Effect on the ability to drive transp. cf. and fur:Caution should be used in case of adverse reactions affecting the speed of psychomotor reactions (dizziness, fatigue, malaise).

Form release / dosage:

Tablets, film-coated 10 mg, 20 mg and 40 mg.

Packaging:

10 tablets per blister Aluminum foil / Aluminum foil.

By 1, 2, 3, 6, 9 or 10 blisters with instructions for use in a cardboard box.

Storage conditions:

At a temperature of no higher than 25 ° C. Keep out of the reach of children!

Shelf life:

2 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-000835

Date of registration:10.10.2011

The owner of the registration certificate:AKTAVIS, LTD. AKTAVIS, LTD. Russia

Manufacturer: & nbsp

ACTAVIS hf. Iceland

Representation: & nbspACTAVIS GROUP AO ACTAVIS GROUP AO Iceland

Information update date: & nbsp30.10.2014

Illustrated instructions

Instructions

Torvalip (Torvalip)