Atorvastatin-SZ pills 40mg 30pcs

Composition

Film-coated tablets of pink color, round, biconvex; on a cross-section, the tablet core is white or almost white in color.

1 tab. atorvastatin (in the form of a calcium salt)10 mg

Excipients:

lactose monohydrate (milk sugar) – 62 mg,

calcium carbonate-33 mg,

povidone K 30 (polyvinylpyrrolidone medium molecular weight) – 6 mg,

croscarmellose sodium (primellose) – 6.75 mg,

sodium stearyl fumarate-1.5 mg,

colloidal silicon dioxide (aerosil) – 0.75 mg,

microcrystalline cellulose-30 mg.

Shell composition:

Opadray II (polyvinyl alcohol, partially hydrolyzed – 2.2 mg, macrogol (polyethylene glycol) 3350 – 0.6175 mg, talc – 1 mg, titanium dioxide (E171) – 0.9585 mg, soy lecithin (E322) – 0.175 mg, aluminum varnish based on indigo carmine dye – 0.003 mg, aluminum varnish based on azorubin dye – 0.0255 mg, aluminum varnish based on crimson dye [Ponso 4R] – 0.0205 mg).

Pharmacological action

Atorvastatin is a selective competitive inhibitor of HMG-CoA reductase, a key enzyme that converts 3-hydroxy-3-methylglutaryl-CoA to mevalonate, a precursor of steroids, including cholesterol; a synthetic lipid-lowering agent.

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

Atorvastatin reduces the concentration of cholesterol and lipoproteins in blood plasma, inhibiting HMG-CoA reductase and cholesterol synthesis in the liver and increasing the number of” hepatic ” LDL receptors on the cell surface, which leads to increased uptake and catabolism of LDL-C.

Atorvastatin reduces the formation of LDL-C and the number of LDL particles, causes a pronounced 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 agents.

Atorvastatin in doses from 10 mg to 80 mg reduces the concentration of cholesterol by 30% – 46%, LDL-C – by 41% – 61%, apolipoproteins-on-B-by 34% – 50% and TG-by 14% – 33%. The results of therapy are similar in patients with heterozygous familial hypercholesterolemia, non-familial forms of hypercholesterolemia and mixed hyperlipidemia, including patients with type 2 diabetes mellitus.

In patients with isolated hypertriglyceridemia, atorvastatin reduces the concentration of cholesterol, LDL-C, VLDL-C, apo-B and TG and increases the concentration of HDL-C. In patients with dysbetalipoproteinemia, atorvastatin reduces the concentration of intermediate-density lipoprotein cholesterol.

In patients with hyperlipoproteinemia of type IIa and IIb according to the Fredrickson classification, the average increase in HDL-C concentration during treatment with atorvastatin (10-80 mg) compared to baseline is 5.1% – 8.7% and does not depend on the dose. There is a significant dose-dependent decrease in the total cholesterol/HDL-C and LDL-C/HDL-C ratios by 29% -44% and 37% -55%, respectively.

The antisclerotic effect of atorvastatin is a consequence of its effect on the walls of blood vessels and blood components. Atorvastatin inhibits the synthesis of isoprenoids, which are growth factors of cells of the inner lining of blood vessels. Under the action of atorvastatin, endothelium-dependent dilation of blood vessels improves, the concentration of LDL-C, apolipoprotein B, and TG decreases, and the concentration of HDL-C cholesterol and apolipoprotein A increases.

Atorvastatin reduces the viscosity of blood plasma and the activity of certain clotting and platelet aggregation factors. Thanks to this, it improves hemodynamics and normalizes the state of the coagulation system. HMG-CoA reductase inhibitors also have an effect on macrophage metabolism, block their activation and prevent the rupture of atherosclerotic plaque.

Atorvastatin-SZ at a dose of 80 mg significantly reduces the risk of ischemic complications and mortality by 16% after a 16-week course, and the risk of repeated hospitalization for angina accompanied by signs of myocardial ischemia by 26%. In patients with different baseline LDL-C concentrations, Atorvastatin-SZ reduces the risk of ischemic complications and mortality (in patients with non-Q-wave myocardial infarction and unstable angina, as well as in men and women, and in patients younger and older than 65 years).

A decrease in the concentration of LDL-C in the blood plasma correlates better 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 the section “Dosage and use”).

The therapeutic effect is achieved 2 weeks after the start of therapy, reaches a maximum in 4 weeks and persists throughout the entire period of therapy.

Pharmacokinetics:

Suction

Atorvastatin is rapidly absorbed after oral use: the time to reach its maximum concentration (TCmax) in blood plasma is 1-2 hours. In women, the maximum concentration (Cmax) of atorvastatin is 20% higher, and the area under the concentration-time curve (AUC) is 10% lower than in men. The degree of absorption and plasma concentration increase in proportion to the dose.

The absolute bioavailability is about 14%, and the systemic bioavailability of HMG-CoA reductase inhibitory activity is about 30%. Low systemic bioavailability is due to presystemic metabolism in the gastrointestinal mucosa and/or during “primary passage” through the liver. Food intake reduces the rate and degree of drug absorption (by 25% and 9%, respectively), as evidenced by the results of determining Cmax and AUC, but the decrease in LDL-C is similar to that when taking atorvastatin on an empty stomach. Despite the fact that after taking atorvastatin in the evening, its plasma concentration is lower (Cmax and AUC, approximately 30%) than after taking it in the morning, the decrease in LDL-C concentration does not depend on the time of day at which the drug is taken.

Distribution

The average volume of distribution of atorvastatin is about 381 liters. Binding to plasma proteins is not less than 98%. The ratio of the content in red blood cells/blood plasma is about 0.25, i. e. atorvastatin does not penetrate well into red blood cells.

Metabolism

Atorvastatin is largely metabolized to form ortho – and parahydroxylated derivatives and various beta-oxidation products. In vitro, ortho-and parahydroxylated metabolites have an inhibitory effect on HMG-CoA reductase comparable to that of atorvastatin. Approximately 70% of the decrease in HMG-CoA reductase activity occurs due to the action of active circulating metabolites. The results of initro studies suggest that the liver SURZA 4 isoenzyme plays an important role in the metabolism of atorvastatin. This fact is supported by an increase in the concentration of the drug in blood plasma with simultaneous use of erythromycin, which is an inhibitor of this isoenzyme. In vitro studies have also shown that atorvastatin is a weak inhibitor of the CYP3A4 isoenzyme. Atorvastatin does not have a clinically significant effect on the plasma concentration of terfenadine, which is mainly metabolized by the CYP4A4 isoenzyme, so its significant effect on the pharmacokinetics of other substrates of the CYP4A4 isoenzyme is unlikely (see the section “Interaction with other drugs”).

Deduction

Atorvastatin and its metabolites are mainly excreted in the bile after hepatic and / or extrahepatic metabolism (atorvastatin does not undergo pronounced enterohepatic recirculation). The half-life (T1 / 2) of atorvastatin 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 persists for about 20-30 hours due to their presence. After oral use, less than 2% of the drug dose is detected in the urine.

Special patient groups

Elderly patients

Plasma concentrations of atorvastatin in patients over 65 years of age are higher (Cmax by about 40%, AUC by about 30%) than in young adult patients. There were no differences in the efficacy and safety of the drug, or achievement of the goals of lipid-lowering therapy in elderly patients compared to the general population.

Children

Pharmacokinetic studies of the drug in children have not been conducted.

Renal insufficiency

Impaired renal function does not affect the concentration of atorvastatin in blood plasma or its effect on lipid metabolism, and therefore no dose change is required in patients with impaired renal function.

Atorvastatin is not eliminated during hemodialysis due to intensive binding to plasma proteins.

No studies have been conducted on the use of atorvastatin in patients with end-stage renal failure.

Liver failure

The concentration of the drug is significantly increased (Cmax approximately 16 times, AUC approximately 11 times) in patients with alcoholic cirrhosis of the liver (stage B on the Child-Pugh scale) (see the section “Contraindications”).

Indications

— in combination with diet to reduce elevated levels of total Cholesterol, Cholesterol-LDL, and apolipoprotein b and triglycerides and improve HDL-C in patients with primary hypercholesterolemia, heterozygous familial and non-family hypercholesterolemia and combined (mixed) hyperlipidemia (types IIa and IIb according to Fredrickson);

— in combination with diet for the treatment of patients with elevated serum TG levels (type IV according to Fredrickson) and patients with dysbetalipoproteinemia (type III Fredrickson), whose diet does not provide an adequate effect;

— to reduce the levels of total Cholesterol and Cholesterol-LDL in patients with homozygous familial hypercholesterolemia when diet and other non-pharmacological therapies are not sufficiently effective.

Contraindications

active liver disease;

— increased activity of liver enzymes of unknown origin (more than 3 times compared to the ULN);

— liver failure (classes A and b according to child-Pugh);

— pregnancy;

— lactation period;

— age under 18 years (effectiveness and safety not established);

— hypersensitivity to the components of the drug.

The drug should be used with caution in patients with chronic alcoholism, a history of liver diseases, severe electrolyte disturbances, endocrine and metabolic disorders, arterial hypotension, severe acute infections (sepsis), uncontrolled epilepsy, extensive surgical interventions, injuries, and skeletal muscle diseases.

Side effects

Nervous system disorders: > 1% >– insomnia, dizziness.

From the side of the senses: < 1% – amblyopia, tinnitus, dry conjunctiva, accommodation disorders, retinal haemorrhage, deafness, glaucoma, parasomia, loss of taste, perversion of taste.

From the cardiovascular system: > 1% – chest pain. >

From the hematopoietic system: < 1% – anemia, lymphoadenopathy, thrombocytopenia.

Respiratory system disorders: > 1% – bronchitis, rhinitis. >

From the digestive system: > 1% – nausea. >

Musculoskeletal disorders: > 1% – arthritis. >

From the genitourinary system: > 1% – urogenital infections, peripheral edema; >

Dermatological reactions: > 1% – alopecia, xeroderma, photosensitization, increased sweating, eczema, seborrhea, ecchymosis, petechiae.

From the endocrine system: < 1% – gynecomastia, mastodynia.

From the side of metabolism: < 1% – increase in body mass, aggravation of gout.

Allergic reactions: < 1% – skin itching, skin rash, contact dermatitis, rarely – urticaria, angioedema, facial edema, anaphylaxis, erythema multiforme (including. Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome).

Laboratory parameters: < 1% – hyperglycemia, hypoglycemia, increased serum CPK, albuminuria.

Interaction

When atorvastatin is co-administered with cyclosporine, HIV protease inhibitors (indinavir, ritonavir), antibiotics (erythromycin, clarithromycin, hinupristin/dalfopristin), antifungal drugs from the azole group (fluconazole, itraconazole, ketoconazole), nefazodone, fibroic acid derivatives, nicotinic acid or diltiazem, the concentration of atorvastatin in the blood is reduced by the following factors: This increases the risk of developing myopathy with rhabdomyolysis and acute renal failure.

When Atorvastatin and a suspension containing magnesium hydroxide and aluminum hydroxide were administered simultaneously, the concentration of atorvastatin in blood plasma decreased by about 35%, but the degree of reduction in LDL-C levels did not change.

When used simultaneously Atorvastatin does not affect the pharmacokinetics of antipyrine (phenazone), so interaction with other drugs metabolized by the same cytochrome P450 isoenzymes is not expected.

With simultaneous use of colestipol, the concentration of atorvastatin in blood plasma decreases by about 25%. However, the lipid-lowering effect of the combination of Atorvastatin and colestipol exceeded that of each drug separately.

With repeated use of digoxin and Atorvastatin at a dose of 10 mg, the Css of digoxin in blood plasma did not change. However, when digoxin was used in combination with Atorvastatin at a dose of 80 mg/day, the digoxin concentration increased by about 20%. When using this combination, the condition of patients should be monitored.

Concomitant use of Atorvastatin and erythromycin (500 mg 4 times / day) or clarithromycin (500 mg 2 times / day), which inhibit the CYP3A4 isoenzyme, an increase in the concentration of atorvastatin in blood plasma was observed.

Concomitant use of Atorvastatin (10 mg 1 time/day) and azithromycin (500 mg 1 time/day) did not change the concentration of atorvastatin in blood plasma.

Atorvastatin did not have a clinically significant effect on the plasma concentration of terfenadine, which is mainly metabolized by CYP3A4; therefore, it seems unlikely that Atorvastatin can significantly affect the pharmacokinetic parameters of other substrates of the CYP3A4 isoenzyme.

When Atorvastatin was co-administered with an oral contraceptive containing norethindrone and ethinylestradiol, there was a significant increase in the AUC of norethindrone and ethinylestradiol by approximately 30% and 20%, respectively. This effect should be considered when choosing an oral contraceptive for a woman receiving Atorvastatin.

Concomitant use with drugs that reduce the concentration of endogenous steroid hormones (including cimetidine, ketoconazole, spironolactone) increases the risk of reducing endogenous steroid hormones (caution is required with these combinations).

When studying the interaction of Atorvastatin with warfarin and cimetidine, no signs of clinically significant interaction were found.

Concomitant use of Atorvastatin 80 mg and amlodipine 10 mg did not alter the pharmacokinetics of atorvastatin at steady state.

There was no clinically significant adverse interaction between Atorvastatin and antihypertensive agents.

Concomitant use of Atorvastatin with protease inhibitors known as CYP3A4 inhibitors (grapefruit juice) has been associated with an increase in the concentration of atorvastatin in blood plasma, and therefore the use of this juice should be avoided.

Concomitant use of Atorvastatin with inducers of the CYP3A4 isoenzyme (efavirenz, rifampicin) leads to a decrease in the concentration of atorvastatin in blood plasma.

Pharmaceutical incompatibilities are not known.

How to take, course of use and dosage

Before prescribing Atorvastatin, the patient should be recommended a standard lipid-lowering diet, which he should follow throughout the entire treatment period.

The drug can be taken at any time of the day with food or regardless of the time of meal. The dose is selected taking into account the initial LDL-C levels, the purpose of therapy, and the individual effect. At the beginning of treatment and/or during an increase in the dose of Atorvastatin, it is necessary to monitor blood lipid levels every 2-4 weeks and adjust the dose accordingly.

The initial dose is on average 10 mg 1 time/day and further varies from 10 mg to 80 mg 1 time/day.

When used concomitantly with cyclosporine, the daily dose of Atorvastatin should not exceed 10 mg.

In primary hypercholesterolemia and mixed hyperlipidemia with elevated serum TG levels (Fredrickson type IV), as well as in dysbetalipoproteinemia (Fredrickson type III) in most cases, it is sufficient to prescribe the drug at a dose of 10 mg 1 time/day. A significant therapeutic effect is usually observed after 2 weeks, and the maximum therapeutic effect is usually observed after 4 weeks. With long-term treatment, this effect persists.

In homozygous familial hypercholesterolemia, the drug is prescribed at a dose of 80 mg (4 tablets of 20 mg) 1 time/day.

In patients with renal insufficiency and kidney diseases the concentration of atorvastatin in the blood plasma does not change, the degree of reduction in LDL-C remains, so a change in the dose of the drug is not required.

In case of hepatic insufficiency, the dose of the drug should be reduced.

When using the drug in elderly patients, there were no differences in the safety, effectiveness or achievement of the goals of lipid-lowering therapy in comparison with the general population.

Overdose

Treatment: there is no specific antidote, and symptomatic therapy is performed. Hemodialysis is ineffective.

Special instructions

Before starting therapy with Atorvastatin, it is necessary to try to achieve control of hypercholesterolemia by adequate diet therapy, increased physical activity, weight loss in obese patients, and treatment of other conditions. Patients should follow a hypocholesterolemic diet during the entire treatment period.

The use of HMG-CoA reductase inhibitors to reduce blood lipids may lead to changes in biochemical parameters that reflect liver function. Liver function should be monitored before starting therapy,6 weeks,12 weeks after starting Atorvastatin and after each dose increase, as well as periodically, for example, every 6 months. An increase in the activity of liver enzymes in the blood serum can be observed during therapy with Atorvastatin. In such cases, the patient’s condition should be monitored until the activity of liver enzymes normalizes. If the ALT or ACT values are more than 3 times the ULN, it is recommended to reduce the dose of Atorvastatin or discontinue treatment. Active liver disease or a persistent increase in the activity of aminotransferases of unknown origin serve as contraindications to the appointment of Atorvastatin.

Treatment with Atorvastatin may cause myopathy. Patients with advanced myalgia, muscle soreness or weakness, and / or a marked increase in CPK activity are likely to develop myopathy (muscle pain and weakness combined with an increase in CPK activity more than 10 times compared to ULN). Atorvastatin therapy should be discontinued if there is a marked increase in CKD activity or if there is a confirmed or suspected myopathy.

The risk of myopathy associated with other drugs in this class was increased with concomitant use of cyclosporine, fibrates, erythromycin, nicotinic acid, or azole antifungal agents. Many of these drugs inhibit CYP3A4-mediated metabolism and / or drug transport. Atorvastatin is biotransformed by CYP3A4. When prescribing Atorvastatin in combination with fibrates, erythromycin, immunosuppressants, azole antifungal agents or nicotinic acid in hypolipidemic doses, the expected benefit and risk of treatment should be carefully weighed and patients should be regularly monitored for muscle pain or weakness, especially during the first months of treatment and during periods of increasing the dose of any drug. In such situations, periodic monitoring of CPK activity can be recommended, although such monitoring 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 have been described. Atorvastatin therapy should be temporarily discontinued or completely discontinued if there are signs of possible myopathy or a risk factor for developing renal failure due to rhabdomyolysis (for example, severe acute infection, hypotension, serious surgery, trauma, severe metabolic, endocrine and electrolyte disorders, and uncontrolled seizures).

Patients should be warned to seek immediate medical attention if they experience unexplained muscle pain or weakness, especially if they experience malaise or fever.

Influence on the ability to drive motor vehicles and manage mechanisms

When driving vehicles or working with machinery, patients should exercise caution, as there is a risk of dizziness when using Atorvastatin.

With impaired renal function

In patients with renal insufficiency and kidney diseases, the concentration of atorvastatin in the blood plasma does not change, the degree of reduction in LDL cholesterol remains, so a change in the dose of the drug is not required.

With impaired liver function

The drug is contraindicated in active liver diseases; increased activity of liver enzymes of unknown origin (more than 3 times compared to ULN); in hepatic insufficiency (classes A and B on the Child-Pugh scale).

In case of hepatic insufficiency, the dose of the drug should be reduced.

Use in children

Contraindicated in children under 18 years of age (efficacy and safety have not been established).

Form of production

Tablets covered with a film-coated pink color, round, biconvex. On a cross-section, the tablet core is white or almost white in color.

Active ingredient

Atorvastatin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Prevention of heart attacks and strokes, Atherosclerosis