Atorvastatin Alkaloid pills 20mg, 30pcs

Composition

One tablet contains:

Active ingredient:

atorvastatin 20 mg (in the form of atorvastatin calcium trihydrate 21.70 mg).

Core:

lactose monohydrate / microcrystalline cellulose (75%: 25%) 128.60 mg;

calcium carbonate 45.28 mg;

copovidone 4.40 mg;

crospovidone 8.80 mg;

croscarmellose sodium 2.20 mg;

sodium lauryl sulfate 4.40 mg;

colloidal silicon dioxide 1.32 mg;

talc 1.10 mg;

magnesium stearate 2.20 mg.

Shell:

Opadry white Y-1-7000 [hypromellose (E 464) – 62,500%; titanium dioxide (E 171) – 31,250%; macrogol 400 – 6,250%] – 5,00 mg.

Pharmacological action of

Pharmacodynamically is a selective competitive inhibitor of HMG-COA reductase -the enzyme that determines the speed limit of cholesterol biosynthesis, is responsible for the conversion of 3-hydroxy-3-methyl-glutaryl-coenzyme A to mevalonate, a precursor of sterols, including cholesterol. In the liver, triglycerides and cholesterol are incorporated into very low-density lipoproteins (VLDL), enter the blood plasma and are transported to peripheral tissues. VLDL forms low-density lipoproteins (LDL), which are catabolized primarily through interaction with high-affinity LDL receptors. Atorvastatin reduces plasma cholesterol and lipoprotein levels by inhibiting HMG-CoA reductase and cholesterol synthesis in the liver, as well as by increasing the number of “hepatic” LDL receptors on the cell surface, increasing the uptake and catabolism of LDL. Atorvastatin reduces LDL production and the number of LDL particles. Atorvastatin causes a pronounced and persistent increase in the activity of LDL receptors in combination with favorable changes in the quality of circulating LDL particles. Dose-dependently reduces LDL levels in patients with homozygous hereditary hypercholesterolemia, resistant to therapy with other lipid-lowering agents. Studies of the dose-effect ratio have shown that atorvastatin reduces the level of total cholesterol (by 30-46%), LDL cholesterol (by 41-61%), apolipoprotein B (by 34-50%) and triglycerides (by 14-33%), while simultaneously causing, to varying degrees, an increase in HDL cholesterol and apolipoprotein A. These results were similar in patients with heterozygous familial hypercholesterolemia, non-familial forms of hypercholesterolemia, and mixed hyperlipidemia, including patients with non-insulin-dependent diabetes mellitus. Due to a decrease in total cholesterol, LDL cholesterol and apolipoprotein B, the risk of cardiovascular diseases decreases and, accordingly, the risk of death decreases. Studies on the effect of atorvastatin on cardiovascular morbidity and mortality have not yet been completed. 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. Pharmacokinetics of absorption After oral use, atorvastatin is rapidly absorbed into the blood. The maximum concentration (Cmax) in blood plasma is reached within 1-2 hours, Cmax in women is 20% higher, the area along the “concentration-time” curve (AUC) is 10% lower; Cmax in patients with alcoholic cirrhosis of the liver increases by 16 times, AUC-by 10 times. Food intake slightly reduces the rate and duration of drug absorption (by 25% and 9%, respectively), but cholesterol reduction is similar to that when taking atorvastatin without food. The absolute bioavailability of atorvastatin is approximately 12%, and the systemic bioavailability, which determines the inhibitory activity against HMG-CoA reductase, is 30%. Low systemic bioavailability is due to presystemic metabolism in the gastrointestinal mucosa and during the” first pass ” through the liver. Distribution The average volume of distribution of atorvastatin is approximately 381 liters. Binding to plasma proteins -98%. Atorvastatin is mainly metabolized in the liver with the participation of cytochrome P 450 isoenzymes CYP3A4, CYP3A5 and CYP3A7 to form pharmacologically active metabolites (ortho – and parahydroxylated derivatives, beta-oxidation products). In vitro, ortho-and parahydroxylated metabolites have an inhibitory effect on HMG-CoA reductase comparable to that of atorvastatin. The inhibitory effect of the drug on HMG-CoA reductase is approximately 70% determined by the activity of circulating metabolites. Excretion Atorvastatin is mainly excreted in bile after hepatic and / or extrahepatic metabolism (it does not undergo pronounced enterohepatic recirculation). The elimination half-life is 14 hours. Inhibitory activity against HMG-CoA reductase persists for about 20-30 hours due to the presence of active metabolites. Less than 2% of the oral dose of the drug is detected in the urine. It is not excreted during hemodialysis.

Indications

• In patients with primary hypercholesterolemia, heterozygous familial and non-family hypercholesterolemia and combined (mixed) hyperlipidemia (types PA and lib at Fredrikson) in combination with diet to reduce elevated levels of total cholesterol, LDL cholesterol, and apolipoprotein b and triglycerides and increasing HDL cholesterol
• for the treatment of patients with elevated serum levels of triglycerides (a type IV Fredrickson) and patients with dysbetalipoproteinemia (type III Fredrickson), whose diet does not provide an adequate effect
• in patients with homozygous familial hypercholesterolemia to reduce levels of total cholesterol and LDL cholesterol, when diet and other non-pharmacological therapies are not sufficiently effective.

Use during pregnancy and lactation

Atorvastatin is contraindicated for use during pregnancy and lactation. It is not known whether atorvastatin is excreted in breast milk. Taking into account the possibility of adverse events in infants, if it is necessary to use the drug during lactation, the question of stopping breastfeeding should be decided. Women of reproductive age should use adequate contraception during treatment. Atorvastatin can only be prescribed to women of reproductive age if the probability of pregnancy is very low and the patient is informed about the possible risk of treatment for the fetus.

Contraindications

• Hypersensitivity to the components of the drug;
• active liver disease or increased activity of “liver” enzymes of unknown origin (more than 3 times compared with the upper limit of normal);
• hepatic failure (severity according to the classification of child-Pugh A and b);
• pregnancy;
• lactation;
• age to 18 years (efficacy and safety not established)

With caution:  alcohol abuse, a history of liver disease, severe electrolyte imbalance, endocrine and metabolic disorders, hypotension, severe acute infections (sepsis), uncontrolled epilepsy, extensive surgery, injuries, skeletal muscle diseases.

Side effects

Most common (1% or more):  insomnia, headache, asthenic syndrome; nausea, diarrhea, abdominal pain, dyspepsia, flatulence, constipation; myalgia. Less frequently (less than 1%): Nervous system disorders:  malaise, dizziness, amnesia, paresthesia, peripheral neuropathy, hypesthesia. From the digestive system:  vomiting, anorexia, hepatitis, pancreatitis, cholestatic jaundice. From the musculoskeletal system:  back pain, muscle cramps, myositis, myopathy, myalgia, arthralgia, rhabdomyolysis. Allergic reactions:  urticaria, pruritus, rash, anaphylaxis, bullous rash, polymorphic exudative erythema (including Stevens-Johnson syndrome), Lyell’s syndrome, angioedema. From the side of hematopoietic organs:  thrombocytopenia. From the side of metabolism:  hypo – or hyperglycemia, increased serum creatine phosphokinase (CPK) activity. Other services:  impotence, peripheral edema, weight gain, chest pain, secondary renal failure, alopecia, tinnitus, fatigue. The most common gastrointestinal side effects are constipation, flatulence, dyspepsia, and abdominal pain; these symptoms usually subside as treatment continues. During clinical trials, drug withdrawal due to side effects was required in less than 2% of patients.

Interaction

The risk of myopathy during treatment with HMG-CoA reductase inhibitors increases when they are used in combination with cyclosporine, fibrates, macrolide antibiotics (including erythromycin), azole antifungal agents or nicotinic acid. In some rare cases, these combinations cause rhabdomyolysis, accompanied by renal failure due to myoglobinuria. In this regard, a careful assessment of the risk-benefit ratio of combined treatment is necessary (see the section “Special instructions”). Inhibitors of the cytochrome P 450 CYP-4 isoenzyme atorvastatin is metabolized with the participation of the cytochrome P 450 CYP-3 and 4 isoenzyme. When atorvastatin is used in combination with inhibitors of the cytochrome P 450 CYP-4 isoenzyme (for example, cyclosporine, macrolide antibiotics, for example, erythromycin and clarithromycin, nefazodone, azole antifungal drugs, for example, itraconazole, and HIV protease inhibitors) drug interactions may occur. With the combined use of drugs, increased plasma concentrations of atorvastatin may occur. In this regard, special care should be taken when using atorvastatin in combination with the above-mentioned drugs (seesection “Special instructions”). 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 should be exercised). R-glycoprotein inhibitors Atvastatin and its metabolites are substrates for P-glycoprotein. P-glycoprotein inhibitors (e. g., cyclosporine) may increase the bioavailability of atorvastatin. Erythromycin, clarithromycinthe concomitant use of atorvastatin and erythromycin (500 mg 4 times/day) or clarithromycin (500 mg 2 times/day), which inhibit cytochrome P450 for 4, increased the concentration of atorvastatin in blood plasma. Concomitant use of atorvastatin (10 mg once daily) and azithromycin (500 bp once daily) did not change the concentration of atorvastatin in the blood plasma. Itraconazole When combined with atorvastatin at a dose of 40 mg and itraconazole at a dose of 200 mg once a day, an increase in AUC was detected to a level that exceeded the norm by three times. Protease inhibitors Simultaneous use of atorvastatin with protease inhibitors, known as cytochrome P450-4 inhibitors, was accompanied by an increase in the concentration of atorvastatin in blood plasma. Grapefruit Juice Grapefruit juice contains at least one ingredient that is a CYP3A4 inhibitor, and may cause an increase in plasma concentrations of those drugs that are metabolized by CYP3A4. A daily intake of 240 ml of grapefruit juice increased the AUC of atorvastatin by 37% and decreased the AUC of the active orthohydroxy metabolite by 20.4%. Consumption of large amounts of grapefruit juice (more than 1.2 liters per day for 5 days) increased the AUC of atorvastatin by 2.5 times, and the AUC of active HMG-CoA reductase inhibitors (atorvastatin + its metabolites)-by 1.3 times. In this regard, the consumption of large amounts of grapefruit juice during treatment with atorvastatin is not recommended. Cytochrome P 450 inducers. The effect of drugs that induce the cytochrome P 450 CYP-4 isoenzyme (for example, rifampicin and phenazone) on atorvastatin is unknown. Interactions with atorvastatin and other substrates of this isoenzyme are unknown; however, the possibility of these interactions should be considered when using drugs with a low therapeutic index – in particular, class III antiarrhythmics, for example, amiodarone. Gemfibrozil / Fibraty Risk of myopathy caused by atorvastatin may increase with concomitant use of fibrates. In vitro studies indicate that gemfibrozil may also interact with atorvastatin by inhibiting eiro glucuronidation, which may cause an increase in plasma concentrations of atorvastatin (see section “Special instructions”). Digoxin With repeated use of digoxin and atorvastatin at a dose of 10 mg, the steady-state plasma concentrations of digoxin 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%. Patients receiving digoxin in combination with atorvastatin should be monitored. Oral contraceptives Taking atorvastatin in combination with an oral contraceptive containing norethisterone and ethinyl estradiol caused an increase in plasma concentrations of norethisterone and ethinyl estradiol. These increases in concentrations should be considered when selecting oral contraceptive doses. When atorvastatin was co-administered with an oral contraceptive containing norethisterone and ethinylestradiol, there was a significant increase in the AUC of norethisterone and ethinylestradiol by approximately 30% and 20%, respectively. This effect should be considered when choosing an oral contraceptive for a woman receiving atorvastatin. Colestipol When colestipol was administered in combination with atorvastatin, a decrease in the concentration of atorvastatin in blood plasma by approximately 25% was noted. However, when combined with atorvastatin and colestipol, the effect on lipids was more pronounced than when using each of these drugs separately. Antacids: concomitant oral use of atorvastatin and a suspension containing magnesium and aluminum hydroxide reduced the plasma concentration of atorvastatin by approximately 35%; however, the degree of reduction in LDL levels did not change. Warfarin When taking atorvastatin in combination with warfarin, there was a slight decrease in prothrombin time in the first days of taking atorvastatin; however, in the next 15 days, the prothrombin time indicator returned to normal. However, if atorvastatin and warfarin are co-administered, patients should be carefully monitored. Phenazone Concomitant use of atorvastatin does not affect the pharmacokinetics of phenazone, so interaction with other agents metabolized by the same cytochrome isoenzymes is not expected. Cimetidinethe study of combined use of cimetidine and atorvastatin did not reveal a significant interaction between these drugs. No changes in the pharmacokinetic parameters of atorvastatin at steady state were detected when 80 mg of atorvastatin and 10 mg of amlodipine were co-administered. There was also no clinically significant adverse interaction between atorvastatin and antihypertensive agents. Interaction studies with all specific drugs have not been conducted. Atorvastatin did not have a clinically significant effect on the plasma concentration of terfenadine, which is mainly metabolized by cytochrome P450-4; therefore, it seems unlikely that atorvastatin can significantly affect the pharmacokinetic parameters of other cytochrome p450-4 substrates.

How to take, course of use and dosage

Usually, the initial dose is 10 mg once a day. The dose varies from 10 to 80 mg / day. The drug can be taken at any time of the day once a day, regardless of food intake. Doses should be selected individually, taking into account the initial LDL cholesterol level, the purpose of therapy, and the patient’s response to treatment. At the beginning and/or during an increase in the dose of Atorvatatin, it is necessary to monitor blood lipid levels every 2-4 weeks and adjust the dose accordingly. Dose adjustments should be made at intervals of at least 4 weeks. The maximum daily dose is 80 mg. For patients with established coronary heart disease (CHD) and other patients at high risk of cardiovascular complications, the following lipid correction targets are recommended: LDL cholesterol less than 3.0 mmol/L (or less than 115 mg/dl) and total cholesterol less than 5.0 mmol/L (or less than 190 mg/dl). Primary hypercholesterolemia and combined (mixed) hyperlipidemia In most patients, the necessary control of lipid levels is provided by taking 10 mg of Atorvastatin once a day. A significant therapeutic effect is usually observed after 4 weeks. With long-term treatment, this effect persists. Heterozygous familial hypercholesterolemia. Treatment of patients should begin with the appointment of 10 mg of Atorvastatin per day. Individual dose adjustments should be made every 4 weeks to 40 mg / day. After that, you can increase the dose to a maximum level of 80 mg / day, or use a combined appointment of 40 mg of Atorvastatin and bile acid sequestrant. Homozygous familial hypercholesterolemia is prescribed at a dose of 80 mg once a day. In patients with renal insufficiency. Renal diseases do not affect the concentration of atorvastatin in blood plasma or the degree of lipid reduction during its use; therefore, no dose adjustment is required in patients with kidney disease. In patients with hepatic insufficiency. In case of hepatic insufficiency, it may be necessary to reduce the dose or cancel the drug (see the section “Special instructions”).

Overdose

There is no specific antidote. In case of overdose, the necessary symptomatic and supportive therapy should be provided. Monitoring of liver function and serum creatinine clearance is necessary. Hemodialysis is ineffective.

Special instructions

Before starting therapy with Atorvastatin, the patient should be prescribed a standard hypocholesterolemic diet, which he must follow during the entire treatment period. The use of HMG-CoA reductase inhibitors to reduce blood lipids may lead to changes in biochemical parameters that affect 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. Patients with elevated enzyme levels should be monitored until their enzyme levels return to normal. In case of persistent increase in alanine aminotransferase (ALT) or aspartate aminotransferase (ACT) values to a level exceeding more than 3 times the upper permissible limit, it is recommended to reduce the dose of Atorvastatin or discontinue treatment. Atorvastatin should be used with caution in patients who abuse alcohol and / or have liver disease. 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, as with other HMG-CoA reductase inhibitors, may cause myopathy. The diagnosis of myopathy (muscle pain and weakness combined with an increase in creatine phosphokinase (CPK) activity more than 10 times higher than the upper limit of normal) should be discussed in patients with advanced myalgia or muscle weakness and/or a pronounced increase in CPK activity. Patients should be warned that they should immediately inform the doctor about the appearance of unexplained pain or weakness in the muscles, if they are accompanied by malaise or fever.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 cytochrome P450-4-mediated metabolism and / or drug transport. Atorvastatin is biotransformed by CYP in 4 seconds. When prescribing atorvastatin in combination with fibrates, erythromycin, immunosuppressive agents, azole antifungal agents or nicotinic acid in hypolipidemic doses, the risk and expected benefit of treatment should be carefully evaluated 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). 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. No adverse effects of atorvastatin on the ability to drive or operate machinery have been reported.

Storage conditions

At a temperature not exceeding 30 ° C. Keep out of reach of children.

Shelf

life is 2 years.

Active ingredient

Atorvastatin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Atherosclerosis, Prevention of heart attacks and strokes