Atorvastatin-ALSI pills 40mg, 30pcs

Composition

1 film coated tablet contains:

Active ingredient:

atorvastatin calcium trihydrate – 43.4 mg, which corresponds to 40 mg of atorvastatin;

excipients:

calcium carbonate 35.4 mg,

microcrystalline cellulose 24.0 mg,

StarCap 1500 [corn starch and pre-gelatinized starch] 53.6 mg,

colloidal silicon dioxide (aerosil) 400 mcg,

talc 1.6 mg,

magnesium stearate 1.6 mg,

opadray II (series 85) (polyvinyl alcohol 2.56 mg, macrogol 1.29 mg, talc 0.94 mg, titanium dioxide 1.56 mg, iron oxide yellow dye 0.032/ mg, iron oxide red dye 0.00128 mg) 6.4 mg

Pharmacological action

Hypolipidemic agent from the statin group. Selective competitive inhibitor of HMG-CoA reductase, an enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonic acid, a precursor of sterols, including cholesterol. Triglycerides (TG) and cholesterol in the liver are incorporated into very low-density lipoproteins (VLDL), enter the blood plasma and are transported to peripheral tissues. Low-density lipoproteins (LDL) are formed from VLDL during interaction with LDL receptors. Atorvastatin reduces plasma cholesterol and lipoprotein levels by inhibiting HMG-CoA reductase, cholesterol synthesis in the liver, and an increase in the number of “hepatic” LDL receptors on the cell surface, which leads to increased LDL uptake and catabolism. Reduces the formation of LDL, causes a pronounced and persistent increase in the activity of LDL receptors. Reduces LDL levels in patients with homozygous familial hypercholesterolemia, which usually does not respond to treatment with lipid-lowering agents. Reduces the level of total cholesterol by 30-46%, LDL-by 41-61%, apolipoprotein B-by 34-50% and TG-by 14-33%; causes an increase in the level of HDL cholesterol (high-density lipoproteins) and apolipoprotein A. Dose-dependent reduces the level of LDL in patients with homozygous hereditary hypercholesterolemia, resistant to therapy with other lipid-lowering agents.

Indications

Atorvastatin is used:

• in conjunction with diet to reduce elevated levels of total cholesterol, cholesterol/LDL, and apolipoprotein b and triglycerides and increasing HDL cholesterol 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 triglyceride levels (type IV according to Fredrickson) and patients with dysbetalipoproteinemia (type III Fredrickson), whose diet does not provide an adequate effect;
• to reduce levels of total cholesterol and cholesterol/LDL in patients with homozygous familial hypercholesterolemia when diet and other non-pharmacological therapies are not sufficiently effective

Recommendations for use

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

The initial dose is on average 10 mg 1 time/day. The dose varies from 10 to 80 mg 1 time/day. The maximum daily dose of the drug is 80 mg.

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 cholesterol/LDL 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. To ensure the following dosage regimen, it is possible to use Atorvastatin in a different dosage form: film-coated tablets of 10 and 20 mg.

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

Primary hypercholesterolemia and mixed hyperlipidemia

In most cases, it is sufficient to prescribe a dose of 10 mg of Atorvastatin once a day. A significant therapeutic effect is observed after 2 weeks, as a rule, and the maximum therapeutic effect is usually observed after 4 weeks. With long-term treatment, this effect persists.

The use of the drug in patients with renal insufficiency and kidney diseases does not affect the level of Atorvastatin in blood plasma or the degree of reduction in cholesterol/LDL when it is used, so a change in the dose of the drug is not required.

In case of hepatic insufficiency, the dose should be reduced (see the section “With caution” and “Special instructions”).

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.

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 classification child-Pyuga A and b);
• pregnancy;
• lactation;
• age to 18 years (efficacy and safety not established).

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

Side effects

From the nervous system-more often 1% – insomnia, dizziness; less often 1% – headache, asthenia, malaise, drowsiness, nightmares, paresthesia, peripheral neuropathy, amnesia, emotional lability, ataxia, facial nerve paralysis, hyperkinesis, depression, hyperesthesia, loss of consciousness.

From the sensory organs: less than 1% – amblyopia, ringing in the ears, dry conjunctiva, impaired accommodation, hemorrhage in the eyes, deafness, glaucoma, parosmia, loss of taste sensations, perversion of taste.

From the cardiovascular system: more often 1% – chest pain; less often 1% – palpitation, vasodilation, migraine, orthostatic hypotension, increased blood pressure, phlebitis, arrhythmia, angina pectoris.

From the hematopoietic system: less than 1% – anemia, lymphadenopathy, thrombocytopenia, leukocyturia.

From the respiratory system: more often 1% – bronchitis, rhinitis; less often 1% – pneumonia, dyspnoea, bronchial asthma, nosebleeds.

From the digestive system: more often 1% – nausea; less often 1% – heartburn, constipation or diarrhea, flatulence, gastralgia, abdominal pain, anorexia, decreased or increased appetite, dry oral mucosa, belching, dysphagia, vomiting, stomatitis, esophagitis, glossitis, erosive and ulcerative lesions of the oral mucosa, gastroenteritis, hepatitis, biliary colic, cheilitis, ulcer 12-duodenum, pancreatitis, cholestatic jaundice, liver dysfunction, rectal bleeding, melena, bleeding gums, tenesmus.

From the musculoskeletal system: more often 1% – arthritis; less often 1% – leg muscle cramps, bursitis, tendosynovitis, myositis, myopathy, arthralgia, myalgia, rhabdomyolysis, torticollis, muscle hypertonus, joint contractures, joint swelling, tendopathy (in some cases with tendon rupture).

From the genitourinary system: more often 1% – urogenital infections, peripheral edema; less often 1% – dysuria (including pollakiuria, nocturia, urinary incontinence or urinary retention, imperative urge to urinate), nephritis, hematuria, vaginal bleeding, nephrourolithiasis, metrorrhagia, epididymitis, decreased libido, impotence, ejaculation disorders.

From the skin: more often than 1% – alopecia, xeroderma, increased sweating, eczema, seborrhea, ecchymosis, petechiae.

Allergic reactions: less than 1% – pruritus, skin rash, contact dermatitis, rarely-urticaria, angioedema, edema localized in the face, photosensitization, anaphylaxis, erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome).

Laboratory parameters: less than 1% – hyperglycemia, hypoglycemia, increased serum creatinine clearance, albuminuria.

Other: less than 1% – weight gain, gynecomastia, mastodynia, gout exacerbation.

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.

Concomitant oral administration of Atorvastatin and a suspension containing magnesium and aluminum hydroxide reduced plasma concentrations of Atorvastatin by approximately 35%, but the degree of reduction in LDL/cholesterol levels did not change.

Concomitant use of Atorvastatin does not affect the pharmacokinetics of antipyrine, so interaction with other agents metabolized by the same cytochrome isoenzymes is not expected.

Plasma concentrations of Atorvastatin decreased by approximately 25% when colestipol was co-administered. However, the lipid-lowering effect of the combination of Atorvastatin and colestipol exceeded that of each drug separately.

When digoxin and Atorvastatin were re-administered 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.

Concomitant use of Atorvastatin and erythromycin (500 mg 4 times / day) or clarithromycin (500 mg 2 times / day), which inhibit cytochrome P4503A4, an increase in the concentration of Atorvastatin in blood plasma was observed.

Atorvastatin did not have a clinically significant effect on the plasma concentration of terfenadine, which is mainly metabolized by cytochrome P 450 3 A 4; therefore, it seems unlikely that Atorvastatin can significantly affect the pharmacokinetic parameters of other cytochrome P 450 3 A 4 substrates.

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.

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.

Concomitant use of Atorvastatin with protease inhibitors known as cytochrome P4503A4 inhibitors (grapefruit juice) has been associated with increased plasma concentrations of Atorvastatin, and therefore the use of this juice should be avoided.

There was no clinically significant adverse interaction between Atorvastatin and antihypertensive agents, as well as with estrogens. Interaction studies with all specific drugs have not been conducted.

Concomitant use of Atorvastatin with inducers of the CYP3A4 isoenzyme (efavirenz, rifampicin) leads to an increase in the concentration of the drug in blood plasma.

Pharmaceutical incompatibilities are not known.

Overdose

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

Hemodialysis is ineffective.

Description

Round biconvex tablets, covered with a film-coated light yellow color with a brownish tinge. On the cross-section – the inner layer is white or white with a cream tint.

Functional features

Absorption is high. The maximum concentration (Cmax) in blood plasma is reached in 1-2 hours, Cmax in women is 20% higher, the area under the curve/concentration, time (AUC) is 10% lower; Cmax in patients with alcoholic cirrhosis of the liver is 16 times higher, AUC is 11 times higher than normal.

Food slightly reduces the rate and duration of drug absorption (by 25% and 9%, respectively), but the reduction in LDL cholesterol is similar to that when using atorvastatin without food. The concentration of atorvastatin when used in the evening is lower than in the morning (by approximately 30%). A linear relationship was found between the degree of absorption and the dose of the drug.

Absolute bioavailability – 12%, systemic bioavailability of inhibitory activity against HMG-CoA reductase-30%. Low systemic bioavailability is due to presystemic metabolism in the gastrointestinal mucosa and during “primary passage” through the liver.

The average volume of distribution is 381 liters, and the binding to plasma proteins is 98%. It is mainly metabolized in the liver with the participation of cytochrome isoenzymes CYP3A4, CYP3A5 and CYP3A7 with the formation of 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.

Impaired liver function significantly increases (Cmax approximately 16-fold, AUC approximately 11-fold) in patients with alcoholic cirrhosis (Child-Pugh class B); the concentration of atorvastatin in elderly patients over 65 years of age is higher (Cmax approximately 40%, AUC approximately 30%) than in young adult patients; impaired renal function does not affect the concentration of atorvastatin in blood plasma or its effect on the lipid profile, therefore no dose adjustment is required in patients with impaired renal function.

It is excreted in bile after hepatic and / or extrahepatic metabolism (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.

Special instructions

Before starting therapy with Atorvastatin, the patient should be prescribed a standard hypocholesterol 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 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. Patients with elevated enzyme activity should be monitored until their enzyme levels return to normal. If the values of alanine aminotransferase (ALT) or asparagine aminotransferase (AST) are more than 3 times higher than 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 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, muscle soreness or weakness, and/or a marked 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 during treatment with other drugs in this class was increased with concomitant use of cyclosporine, fibrates, erythromycin, nicotinic acid, or antifungal agents derived from azole. Many of these drugs inhibit cytochrome P450-3A4-mediated metabolism and / or drug transport. Atorvastatin is biotransformed by CYP 3A4. When prescribing Atorvastatin in combination with fibrates, erythromycin, immunosuppressive agents, antifungal agents, azole derivatives 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).

Before starting therapy with Atorvastatin, it is necessary to try to achieve control of hypercholesterolemia through adequate diet therapy, increased physical activity, weight loss in obese patients, and treatment of other conditions.

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

Influence on the ability to drive a car and work with mechanisms

When driving a car and working with mechanisms, you should be careful, because there is a risk of developing dizziness.

Storage conditions

Store in a dry place protected from light at a temperature not exceeding 25 ° C.

Keep out of reach of children.

Shelf

life is 3 years. Do not use after the expiration date indicated on the package.

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