Atorvastatin pills 10mg, 90pcs

Composition

1 tablet contains:

Active ingredient:

atorvastatin calcium trihydrate (based on atorvastatin) – 10.00 mg;

excipients:

microcrystalline cellulose-49.68 mg,

lactose monohydrate-40.00 mg,

calcium carbonate-33.00 mg,

crospovidone-7.50 mg,

sodium carboxymethyl starch (sodium starch glycolate) – 4.50 mg,

hyprolose (hydroxypropylcellulose) – 3.00 mg,

magnesium stearate-1.50 mg;

film coating:

[hypromellose – 2,250 mg, talc – 0,882 mg hyprolose (hydroxypropyl cellulose) – 0,873 mg, titanium dioxide – 0,495 mg] or [dry mix for film coating containing hypromellose (50,0%), talc (19,6%), hyprolose of (hydroxypropyl) (19,4%), titanium dioxide (11,0%)] – 4,500 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 total cholesterol (Ch), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (apo-B), as well as very low-density lipoprotein (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, 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 to 80 mg reduces the concentration of total cholesterol by 30-46%, LDL-C  by 41-61%, apo-B  by 34-50% and TG  by 14-33%. The results of therapy are similar in patients with heterozygous familial hypercholesterolemia, non-familial forms of hypercholesterolemia and mixed hyperlipidemia, including patients with type 2 diabetes mellitus.

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

In patients with hyperlipoproteinemia 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 the initial indicator 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.

Atorvastatin 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 (non-Q-wave myocardial infarction and unstable angina, men and women, in patients younger and older than 65 years) atorvastatin reduces the risk of ischemic complications and mortality.

A decrease in the concentration of LDL-C in the blood plasma correlates better with the dose of atorvastatin 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.

Indications

• primary hypercholesterolemia (heterozygous familial and non-familial hypercholesterolemia (Fredrickson type IIa);
• combined (mixed) hyperlipidemia (Fredrickson types IIa and IIb);
• dysbetalipoproteinemia (Fredrickson type III) (as an adjunct to diet);
• familial endogenous hypertriglyceridemia (Fredrickson type IV), resistant to the diet; 
• homozygous familial hypercholesterolemia with the ineffectiveness of diet therapy and other non-pharmacological methods of treatment;
• primary prevention of cardiovascular events in patients without clinical signs of coronary artery disease (ischemic heart disease), but with multiple risk factors for its development over 55 years of age, nicotine dependence, hypertension, diabetes mellitus, genetic predisposition, including on the background of dyslipidemia;
• secondary prevention of cardiovascular events in patients with coronary artery disease to reduce total mortality, myocardial infarction, stroke, re-hospitalization for about angina and the need for revascularization.

Contraindications

• hypersensitivity to any of the components of the drug; 
• liver disease in the active stage;
• increased activity of “liver” transaminases in the blood plasma of unknown origin more than 3 times compared with the upper limit of normal;
• diseases of skeletal muscle;
• lactase deficiency, lactose intolerance, a syndrome of glucose-galactose malabsorption;
• pregnancy and lactation;
• the age of 18 (insufficient clinical data on efficacy and safety for this age group).

With caution

Use in patients who abuse alcohol or in patients with a history of liver disease.

Side effects

World Health Organization (WHO) classification of side effects: very common – ≥1/10, common – ≥1/100 to <1/10, uncommon – ≥1/1000 to <1/100, rare – ≥1/10000 to <1/1000, very rare – Nervous system disorders:  often – insomnia, headache, dizziness, paresthesia, asthenic syndrome; infrequently-peripheral neuropathy, amnesia, hypesthesia.

From the side of the senses:  infrequently-tinnitus; rarely-nasopharyngitis, nosebleeds.

From the cardiovascular system:  palpitations, symptoms of vasodilation, migraines, postural hypotension, high blood pressure, phlebitis, arrhythmia.

From the hematopoietic system:  infrequently-thrombocytopenia.

Respiratory system disorders:  often-chest pain.

From the digestive system:  often – nausea, diarrhea, abdominal pain, dyspepsia, constipation, flatulence (bloating); infrequently-impaired taste perception, vomiting, pancreatitis; rarely-hepatitis, cholestatic jaundice.

Musculoskeletal and connective tissue disorders:  often – myalgia, arthralgia, back pain, joint swelling; infrequently-myopathy, muscle cramps; rarely-myositis, rhabdomyolysis, tendopathy (in some cases with tendon rupture).

From the genitourinary system:  infrequently – sexual dysfunction, secondary renal failure.

From the side of the skin:  often – skin rash, pruritus; infrequently – urticaria; very rarely-angioedema, alopecia, bullous rash, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Allergic reactions:  often-allergic reactions; very rarely-anaphylaxis.

Laboratory parameters:  infrequently-increased activity of aminotransferases( AST, ALT), increased activity of serum creatine phosphokinase (CPK); very rarely – hypoglycemia, hyperglycemia. Other services:  often-peripheral edema; infrequently-weakness, fatigue, fever, anorexia, weight gain.

During post-marketing use of statins, including atorvastatin, it was reported the following side effects: loss or memory loss, depression, sleep disturbances, including insomnia and “nightmare” dreams, sexual dysfunction, gynecomastia, hyperglycemia, increasing the concentration of glycosylated hemoglobin, isolated cases of interstitial lung disease (especially with prolonged use), cases of necrotizing immune-mediated myopathy, and thrombocytopenia.

Interaction

The risk of developing myopathy with rhabdomyolysis and renal failure during treatment with HMG-CoA reductase inhibitors increases when used simultaneously with cyclosporine, antibiotics (erythromycin, clarithromycin, hinupristin/dalfopristin), HIV protease inhibitors (indinavir, ritonavir), antifungal drugs (fluconazole, itraconazole, ketoconazole), nefazodone. All these drugs inhibit the CYP3A4 isoenzyme, which is involved in the metabolism of atorvastatin in the liver.

A similar interaction is possible with the simultaneous use of atorvastatin with fibrates and nicotinic acid in lipid-lowering doses (more than 1 g per day).

When used concomitantly with HIV protease inhibitors, hepatitis C inhibitors, clarithromycin and itraconazole, caution should be exercised and the lowest effective dose of atorvastatin should be used.

Inhibitors of the CYP3A4 isoenzyme Since atorvastatin is metabolized by the CYP3A4 isoenzyme, co-use of atorvastatin with inhibitors of the CYP3A4 isoenzyme may lead to an increase in the concentration of atorvastatin in blood plasma. The degree of interaction and the potentiation effect are determined by the variability of exposure to the CYP3A4 isoenzyme.

Inhibitors of the OATP transport protein 1 In 1 Atorvastatin and its metabolites are substrates of the OATP 1-In-1 transport protein. OATP 1-In-1 inhibitors (for example, cyclosporine) can increase the bioavailability of atorvastatin.

Erythromycin/Clarithromycin Concomitant use of atorvastatin and erythromycin or clarithromycin, which inhibit the CYP3A4 isoenzyme, resulted in increased plasma concentrations of atorvastatin.

Protease inhibitors Concomitant use of atorvastatin with protease inhibitors, known as CYP3A4 inhibitors, is accompanied by an increase in the concentration of atorvastatin in blood plasma.

Diltiazem Concomitant use of atorvastatin 40 mg with diltiazem 240 mg leads to an increase in the concentration of atorvastatin in blood plasma. Itraconazole Concomitant use of atorvastatin and itraconazole resulted in an increase in the concentration of atorvastatin in blood plasma.

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

Inducers of the CYP3A4 isoenzyme Co-use of atorvastatin with inducers of the CYP3A4 isoenzyme (for example, efavirenz, phenytoin or rifampicin) may lead to a decrease in the concentration of atorvastatin in blood plasma. Due to the dual mechanism of interaction with rifampicin (an inducer of the CYP3A4 isoenzyme and an inhibitor of the hepatocyte transport protein OATP 1 In 1), simultaneous use of atorvastatin and rifampicin is recommended, since delayed use of atorvastatin after taking rifampicin leads to a significant decrease in the concentration of atorvastatin in blood plasma.

Antacids Concomitant oral use of atorvastatin and a suspension containing magnesium and aluminum hydroxides reduces the concentration of atorvastatin in blood plasma.

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

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

Digoxin When using digoxin in combination with atorvastatin at a dose of 80 mg/day, the concentration of digoxin increased by about 20%, so such patients should be monitored.

Oral contraceptives When atorvastatin is used simultaneously with an oral contraceptive containing norethisterone and ethinyl estradiol, it is possible to increase the absorption of contraceptives and increase their concentration in blood plasma. This effect should be considered when choosing an oral contraceptive for a woman taking atorvastatin. Terfenadine Concomitant use of atorvastatin did not have a clinically significant effect on the pharmacokinetics of terfenadine.

Warfarin Concomitant use of atorvastatin with warfarin may increase the effect of warfarin on blood clotting parameters in the first days (reduction of prothrombin time). This effect disappears after 15 days of simultaneous use of these drugs.

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

Fusidic acid Rhabdomyolysis has been reported in patients treated with atorvastatin and fusidic acid.

Colchicine Myopathy has been reported with concomitant use of atorvastatin and colchicine. Caution should be exercised in combination therapy with these drugs.

Cimetidine When studying the interaction of atorvastatin with cimetidine, no signs of clinically significant interaction were found.

Other concomitant therapy Concomitant use of atorvastatin with drugs that reduce the concentration of endogenous steroid hormones (including cimetidine, ketoconazole, spironolactone) increases the risk of reducing endogenous steroid hormones (caution should be exercised). In clinical trials, atorvastatin was used in combination with antihypertensive agents and estrogens, which were prescribed as replacement therapy; no clinically significant undesirable interaction symptoms were observed. Interaction studies with specific drugs have not been conducted.

How to take, course of use and dosage

Inside. Take at any time of the day, regardless of food intake.

Before starting treatment with Atorvastatin, an attempt should be made to control hypercholesterolemia through diet, exercise, and weight loss in obese patients, as well as treatment of the underlying disease.

When prescribing the drug, the patient should be recommended a standard hypocholesterolemic diet, which he should adhere to throughout the entire period of treatment.

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

The maximum daily dose is 80 mg. At the beginning of treatment and/or during an increase in the dose of Atorvastatin, it is necessary to monitor the concentration of lipids in blood plasma every 2-4 weeks and adjust the dose accordingly.

Primary hypercholesterolemia and combined (mixed) Hyperlipidemia Treatment begins with the recommended starting dose of 10 mg once a day, which is increased after four weeks depending on the patient’s response. The maximum daily dose is 80 mg.

Homozygous familial hypercholesterolemia The dose range is the same as for other types of hyperlipidemia. The initial dose is selected individually depending on the severity of the disease. In most patients with homozygous hereditary hypercholesterolemia, the optimal effect is observed when using the drug in a daily dose of 80 mg (once). Atorvastatin is used as an adjunct therapy to other treatments (plasmapheresis) or as the main treatment if therapy with other methods is not possible.

Caution should be exercised in patients with hepatic impairment (due to delayed elimination of atorvastatin from the body). In this situation, clinical and laboratory parameters should be carefully monitored (regular monitoring of aspartate aminotransferase (ACT) and alanine aminotransferase (ALT) activity). If there is a significant increase in the activity of “hepatic” transaminases, the dose of the drug should be reduced or treatment should be discontinued.

In elderly patients and in patients with kidney disease, the dose of the drug should not be changed. Impaired renal function does not affect the concentration of atorvastatin in blood plasma or the degree of decrease in LDL-C concentration during atorvastatin therapy, so no dose adjustment is required.

Use in combination with other medicinal products If concomitant use with cyclosporine, telaprevir or a combination of tiprapavir/ritonavir is necessary, the dose of the drug should not exceed 10 mg per day.

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

Overdose

Cases of overdose are not described.

In case of overdose, the following general measures are necessary: monitoring and maintaining the vital functions of the body, as well as preventing further absorption of the drug (gastric lavage, taking activated charcoal or laxatives). If myopathy develops, followed by rhabdomyolysis and acute renal failure, the drug should be immediately discontinued and an infusion of diuretic and sodium bicarbonate should be initiated.

Rhabdomyolysis can lead to hyperkalemia, which requires intravenous use of a calcium chloride solution or a calcium gluconate solution, infusion 

 5% dextrose (glucose) solution with insulin, use of potassium exchange resins. Since the drug actively binds to plasma proteins, hemodialysis is not effective.

Special instructions

Before starting therapy with Atorvastatin, the patient should be prescribed a standard hypocholesterolemic diet, which he should follow during the entire treatment period.

If severe adverse effects occur, the use of Atorvastatin should be discontinued.

Effect on the liver As with the use of other lipid-lowering agents of this class, after treatment with atorvastatin, a moderate (more than 3 times higher than the upper limit of normal) increase in the serum activity of “hepatic” transaminases AST and ALT was noted. Increased activity of “hepatic” transaminases was usually not accompanied by jaundice or other clinical manifestations. With a reduction in the dose of atorvastatin, temporary or complete withdrawal of the drug, the activity of” hepatic ” transaminases returned to the initial level. Most patients continued to take atorvastatin at a reduced dose without any clinical consequences.

Before starting therapy,6 weeks and 12 weeks after starting Atorvastatin or after increasing its dose, as well as during the entire course of treatment, it is necessary to monitor liver function indicators. Liver function should also be investigated if there are clinical signs of liver damage. If the activity of “hepatic” transaminases increases, their activity should be monitored until it returns to normal. If the increase in AST or ALT activity is more than 3 times higher than the upper limit of normal, it is recommended to reduce the dose or cancel the drug.

Atorvastatin should be used with caution in patients who consume significant amounts of alcohol and/or have a history of liver disease. Active liver disease or permanently increased activity of “hepatic” transaminases in blood plasma of unknown origin are contraindications to the use of Atorvastatin.

Skeletal muscle effects Myalgia has been reported in patients treated with atorvastatin. The diagnosis of myopathy (muscle pain and weakness combined with an increase in creatine phosphokinase activity by more than 10 times compared to the upper limit of normal) should be assumed in patients with diffuse myalgia, muscle soreness or weakness, and/or a pronounced increase in CK activity. 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 of this class increased with the simultaneous use of cyclosporine, fibrates, erythromycin, nicotinic acid in lipid-lowering doses (more than 1 g/day), nefazodone, certain antibiotics, azole antifungal drugs, HIV protease inhibitors.

Many of these drugs inhibit CYP3A4-mediated metabolism and / or drug transport. It is known that the CYP3A4 isoenzyme is the main liver isoenzyme involved in the biotransformation of atorvastatin. When prescribing Atorvastatin in combination with fibrates, erythromycin, immunosuppressants, azole antifungal drugs or nicotinic acid in lipid-lowering doses, the expected benefit and possible risk should be carefully weighed. 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 of these drugs. If combination therapy is necessary, the possibility of using these drugs in lower initial and maintenance doses should be considered. In such situations, periodic monitoring of CPK activity can be recommended, although such monitoring does not prevent the development of severe myopathy.

Rare cases of rhabdomyolysis with acute renal failure due to myoglobinuria have been reported with atorvastatin, as with other statins. If there are symptoms of possible myopathy or a risk factor for renal failure associated with rhabdomyolysis (for example, severe acute infection, hypotension, extensive surgery, trauma, metabolic, endocrine and water-electrolyte disorders, and uncontrolled seizures), Atorvastatin therapy should be temporarily discontinued or completely discontinued.

In the differential diagnosis of sternal pain, consideration should be given to the possibility of an increase in serum CPK activity when using Atorvastatin.

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

The drug Atorvastatin contains lactose, and therefore its use in patients with lactase deficiency, lactose intolerance and glucose-galactose malabsorption syndrome is contraindicated.

Influence on the ability to drive vehicles and mechanisms

Caution should be exercised when driving vehicles and other technical devices that require increased concentration of attention and speed of psychomotor reactions (risk of dizziness).

Form of production

Film-coated tablets

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