Atorvastatin-LEXVM - instructions for use, dose, side effects, contraindications

lactose monohydrate - 90.5 mg / 90.0 mg, gelatin -1.0 mg / 1.0 mg, polysorbate 80 - 0.8 mg / 0.8 mg, croscarmellose sodium - 3,0 mg / 3.5 mg, microcrystalline cellulose 36 mg / 40 mg, corn starch 80.685 mg / 86.35 mg, magnesium stearate 3.0 mg / 3.0 mg, carbonate calcium-21.5 mg / 21.5 mg.

Sheath: hypromellose 6.0 mg / 6.0 mg, titanium dioxide 2.0 mg / 2.0 mg, propylene glycol 0.08 mg / 0.08 mg, talc 1.2 mg / 1.2 mg.

Description:Capsule-shaped capsules coated with a film coat, white or almost white, smooth on both sides.

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 styrenics, including cholesterol. Triglycerides (TG) and cholesterol in the liver are included in the composition of very low density lipoproteins (VLDL), when synthesized in the liver enter the blood plasma and transported to peripheral tissues. Low density lipoproteins (LDL) are formed from VLDL in the course of interaction with LDL receptors. Reduces the concentration of cholesterol and lipoproteins in the blood plasma due to the inhibition of HMG-CoA reductase, the synthesis of cholesterol in the liver and the increase in the number of "liver" LDL receptors on the cell surface, which leads to increased capture and catabolism of LDL. Reduces the formation of LDL, causes a pronounced and persistent increase in the activity of LDL receptors. Reduces the concentration of LDL in patients with homozygous familial hypercholesterolemia, which usually does not respond to lipid-lowering drugs (LS). In doses of 40 mg reduces the concentration of total cholesterol by 30-46%, LDL by 41-61%, apolipoprotein B by 34-50% and TG by 14-33%; increases the concentration of cholesterol-HDL and apolipoprotein A. Dose-dependently reduces the concentration of LDL in patients with homozygous hereditary hypercholesterolemia, resistant to therapy with other lipid-lowering drugs. Reliably reduces the risk of developing ischemic complications (including the development of death from myocardial infarction), the risk of repeated hospitalization for angina accompanied by signs of myocardial ischemia. Does not have a carcinogenic and mutagenic effect. The therapeutic effect is achieved 2 weeks after the initiation of therapy, reaches a maximum after 4 weeks, and persists throughout the treatment period.

Pharmacokinetics:

Absorption is high. Time to reach the maximum concentration (TCmax) - 1-2 hours, the maximum concentration of the active substances in the blood plasma (Cmah) in women is higher by 20%, the area under the curve "concentration of active substance - time" (AUC) - lower by 10%; FROMmah in patients with alcoholic cirrhosis of the liver 16 times, AUC - And times higher than normal. Food slightly reduces the speed and duration of absorption of the drug (by 25% and 9%, respectively), but the reduction in LDL cholesterol is similar to that with atorvastatin without food. The concentration of atorvastatin when used in the evening is lower than in the morning (about 30%). A linear relationship between the degree of absorption and the dose of the drug has been revealed. Bioavailability is 14%, systemic bioavailability of inhibitory activity against HMG-CoA reductase is 30%. Low systemic bioavailability is due to the pre-systemic metabolism in the gastrointestinal mucosa (GIT) and "first pass" through the liver.

The average volume of distribution is 381 liters, the connection with plasma proteins is more than 98%. Metabolized mainly in the liver under the action of isoenzymes CYP3A4, CYP3A5 and CYP3A7 with the formation of pharmacologically active metabolites (ortho- and para-hydroxylated derivatives, beta-oxidation products). In vitro ortho- and para-hydroxylated metabolites have an inhibitory effect on HMG-CoA reductase, comparable to that of atorvastatin. The inhibitory effect of the drug against HMG-CoA reductase is approximately 70% determined by the activity of circulating metabolites and lasts about 20-30 hours due to their presence. The half-life period (T1 / 2) is 14 hours. It is excreted with bile after hepatic and / or extrahepatic metabolism (it does not undergo significant intestinal hepatic recirculation). Less than 2% of the dose taken internally is determined in the urine.

It is not excreted during hemodialysis due to intensive binding to plasma proteins.

With hepatic insufficiency in patients with alcoholic cirrhosis of the liver (Child-Pug B) Cmah and AUC significantly increased (at 16 and 11 times, respectively).

FROMmah and AUC of the drug in the elderly (65 years older) by 40 and 30%, respectively higher than those in adult patients of young age (of clinical importance does not matter). FROMmah, women 20% higher, and AUC 10% lower than those of men (it has no clinical significance).

Renal failure does not affect the concentration of the drug in the plasma.

Indications:

Primary hypercholesterolemia (heterozygous familial and non-family hypercholesterolemia IIbut of the type); combined (mixed) hyperlipidemia (IIa and IIb type by Fredrickson); with increased content of TG in blood plasma (type IV according to Fredrickson); disbetalipoproteinemia (type III) (as a supplement to the diet); family endogenous hypertriglyceridemia (type IV) only when the diet and other non-pharmacological treatments are not effective enough.

Homozygous hereditary hypercholesterolemia (as an adjunct to hypolipidemic therapy).

Contraindications:

Hypersensitivity to the components of the drug, active liver disease, increased activity of "hepatic" transaminases (more than 3 times compared with the upper limit of the norm), pregnancy, breastfeeding, children under 18 years of age (efficacy and safety not established) .

Carefully:

- Alcoholism, alcohol abuse;

- liver disease in history;

- severe electrolyte imbalance;

- endocrine and metabolic disorders;

- arterial hypotension;

- Severe acute infections (sepsis);

uncontrolled epilepsy;

- extensive surgical interventions;

- injury.

Pregnancy and lactation:

Contraindicated in pregnancy. Women of reproductive age should use reliable methods of contraception. Because cholesterol and substances synthesized from cholesterol are important for fetal development, the potential risk of inhibiting HMG-CoA reductase exceeds the benefit of using the drug during pregnancy. When using mothers in the first trimester of lovastatin (inhibitor of HMG-CoA reductase) with dextroamphetamine, births of children with bone deformity, tracheo-esophageal fistula, and an atresia of the anus are known. In case of pregnancy in the course of therapy, the drug should be stopped immediately, and the patients are warned about the potential risk to the fetus. Excreted in breast milk. For the duration of treatment, breastfeeding should be discontinued.

Dosing and Administration:

Inside, taken at any time of the day, but at the same time, regardless of food intake. Before starting therapy, the patient is prescribed a standard hypocholesterolemic diet for the duration of treatment.

The dose ranges from 10 to 80 mg per day and is selected taking into account the initial concentrations of cholesterol, the purpose of therapy and individual effect.For most patients, the initial dose is 10 mg once a day.

With primary hypercholesterolemia and combined (mixed) hyperlipidemia, 10 mg once a day are prescribed. The effect manifests itself within 2 weeks, the maximum effect is observed within 4 weeks.

In case of liver failure, the dose should be reduced.

With renal failure and in elderly patients, dosage adjustment is not required.

When homozygous familial hypercholesterolemia is used, 40 to 80 mg once a day (lowering the LDL content by 18-45%).

Side effects:

Most often (1% or more): insomnia, headache, asthenic syndrome; nausea, diarrhea, abdominal pain, indigestion, flatulence, constipation; myalgia.

Less often (less than 1%): from the side of the nervous system - malaise, dizziness, amnesia, paresthesia, peripheral neuropathy, hypoesthesia.

From the digestive system: vomiting, anorexia, hepatitis, pancreatitis, cholestatic jaundice.

From the musculoskeletal system: back pain, muscle cramps, myositis, myopathy, arthralgia, rhabdomyolysis.

Allergic reactions: urticaria, itching, skin rash, anaphylaxis, bullous rash, polymorphic exudative erythema (including Stevens-Johnson syndrome), Lyell's syndrome.

From the hematopoiesis: thrombocytopenia.

From the side of metabolism: hypo- or hyperglycemia, increased serum creatine phosphokinase (CK) activity.

Other: impotence, peripheral edema, weight gain, chest pain, secondary renal failure, alopecia, tinnitus.

There are reports of the development of atonic fasciitis in the background of atorvastatin, however, the connection with the drug is possible, but has not been proven to date, the etiology is not known.

Overdose:

Symptoms: development of myopathy with subsequent rhabdomyolysis and acute renal failure. In this case, the drug should be immediately canceled.

Treatment: there is no specific antidote. Symptomatic therapy is performed. Take measures to maintain vital body functions and measures to prevent further absorption of the drug: gastric lavage, the reception of activated charcoal. Because the atorvastatin is largely associated with blood plasma proteins, hemodialysis is ineffective.

Interaction:

With the simultaneous administration of cyclosporine, fibrates, erythromycin, clarithromycin, immunosuppressive,antifungal drugs (related to azoles) and nicotinamide, the concentration of atorvastatin in plasma (and the risk of developing myopathy) is increasing.

With simultaneous use of atorvastatin and erythromycin (500 mg 4 times a day) or clarithromycin (500 mg twice a day), there is an increase in the concentration of atorvastatin in the blood plasma.

Antacids reduce the concentration by 35% (the effect on the content of LDL cholesterol does not change).

With the simultaneous use of atorvastatin (10 mg once a day) and azithromycin (500 mg once a day), the concentration of atorvastatin in the plasma does not change.

Clinically significant interaction is not observed with simultaneous use with warfarin, cimetidine, phenazone.

The simultaneous use of atorvastatin with protease inhibitors, known as isoenzyme inhibitors CYP3A4, is accompanied by an increase in the concentration of atorvastatin in plasma (with simultaneous use with erythromycin CmAtorvastatin increases by 40%).

When digoxin is used in combination with atorvastatin at a dose of 80 mg / day, the digoxin concentration increases by about 20%.

Increases the concentration (when administered with atorvastatin at a dose of 80 mg / day) of oral contraceptives containing norethisterone by 30% and ethinyl estradiol on 20%.

The lipid-lowering effect of the combination with colestipol exceeds that for each drug alone, despite a decrease in the concentration of atorvastatin by 25% when it is used concomitantly with colestipol.

With the simultaneous use of atorvastatin 80 mg and amlodipine 10 mg, the pharmacokinetics of atorvastatin did not change.

Simultaneous 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).

When digoxin is used in combination with atorvastatin at a dose of 80 mg / day, the digoxin concentration is increased by 20%.

Special instructions:

Atorvastatin-LEXVM® can cause an increase in serum CK values, which should be taken into account in the differential diagnosis of chest pain. It should be borne in mind that an increase in CK 10-fold compared with the norm, accompanied by myalgia and muscle weakness may be associated with myopathy, treatment should be discontinued.

Required regularly monitor liver function before treatment,6 and 12 weeks after the start of the drug or after an increase in the dose, and periodically (every 6 months) during the entire period of use (before complete normalization of the condition of patients in whom the activity of "hepatic" transaminases exceed normal ones).

Increase activity "hepatic" transaminases is observed mainly in the first 3 months of the drug. It is recommended to cancel the drug or reduce the dose with increasing activity aspartic aminotransferase (ACT) and alanine aminotransferase (ALT) more than 3 times.

It is necessary to temporarily stop the use of atorvastatin in the development of clinical Symptoms, suggesting the presence of acute myopathy, or in the presence of factors, predisposing to the development of acute renal failure against rhabdomyolysis (severe infections, lower blood pressure, extensive surgery, trauma, metabolic, endocrine or pronounced electrolyte violations). Patients should be warned that they should immediately consult a doctor if there is unexplained pain or weakness in the muscles, especially if they are accompanied by a malaise or fever.The risk of myopathy increases with simultaneous application of cyclosporine, derivatives of fibroic acid, erythromycin, nicotinic acid or azole antifungal drugs.

Effect on the ability to drive transp. cf. and fur:

Information on the possible effect of atorvastatin on the ability to control transport means and mechanisms are not available.

Form release / dosage:

Tablets, film-coated 10 mg, 20 mg.

Packaging:For 10 tablets in blister (contour cell packaging) from Al / Al or Al / PVC. For 3 or 6 blisters are placed in a cardboard box together with instructions for use.

Storage conditions:

In a dry place at a temperature not exceeding 25 ° C. Keep out of the reach of children.

Shelf life:

2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-000072

Date of registration:08.12.2010

The owner of the registration certificate:PROTEK-SVM, LLC PROTEK-SVM, LLC Russia

Manufacturer: & nbsp

ACCURE LABS, Pvt.Ltd. India

Information update date: & nbsp07.05.2015

Illustrated instructions

Instructions

Atorvastatin-LEXMM® (Atorvastatin-LEKSVM®)