fastatorvastatin.com
FASTATORVASTATIN.COM

Atorvastatin

Pharmachologic effect

Hypolipidemic drug from the group of statins. Selective competitive inhibitor of HMG-CoA reductase, an enzyme that converts 3-hydroxy-3-methylglutarylcoenzyme A to mevalonic acid, a precursor of sterols, including cholesterol. Triglycerides and cholesterol in the liver are included in VLDL, enter the blood plasma and are transported to peripheral tissues. LDL is formed from VLDL during interaction with LDL receptors.Atorvastatin reduces plasma concentrations of cholesterol and lipoproteins by inhibiting HMG-CoA reductase, synthesizing cholesterol in the liver and increasing the number of LDL receptors in the liver on the cell surface, which leads to increased uptake and catabolism of LDL.Reduces the formation of LDL, causes a pronounced and persistent increase in the activity of LDL receptors. Reduces LDL in patients with homozygous familial hypercholesterolemia, which usually does not respond to therapy with lipid-lowering drugs.It reduces the concentration of total cholesterol by 30-46%, LDL - by 41-61%, apolipoprotein B - by 34-50% and triglycerides - by 14-33%; causes an increase in the concentration of HDL cholesterol and apolipoprotein A. Dose-dependently reduces the LDL content in patients with homozygous hereditary hypercholesterolemia, resistant to therapy with other lipid-lowering drugs.

Pharmacokinetics

Suction

Absorption is high. Cmax in blood plasma is achieved after 1-2 hours. Food slightly reduces the speed and duration of absorption of the drug (by 25% and 9%, respectively), but the decrease in LDL cholesterol is similar to that with fasting atorvastatin. The concentration of Atorvastatin when applied in the evening is lower than in the morning (approximately 30%). A linear relationship between the degree of absorption and the dose of the drug was revealed. Bioavailability - 12%, systemic bioavailability of inhibitory activity against HMG-CoA reductase - 30%. Low systemic bioavailability due to presystemic metabolism in the gastrointestinal mucosa and during the "first passage" through the liver.

Distribution

The average Vd - 381 liters. Binding to plasma proteins - 98%.

Metabolism

It is metabolized mainly in the liver under the action of cytochrome 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.

Breeding

It is excreted with bile after hepatic and / or extrahepatic metabolism (does not undergo pronounced enterohepatic recirculation). T1 / 2 - 14 hours. The inhibitory activity against HMG-CoA reductase persists for about 20-30 hours due to the presence of active metabolites. Less than 2% of an oral dose is determined in the urine. It is not excreted during hemodialysis. Pharmacokinetics in special patient groups Cmax in women is higher by 20%, AUC - lower by 10%. Cmax in patients with alcoholic cirrhosis is 16 times higher, AUC - 11 times higher than normal.

Indications for Atorvastatin

Atorvastatin is used:

in combination with a diet to reduce elevated levels of total cholesterol, cholesterol / LDL, apolipoprotein B and triglycerides and increase the concentration of HDL cholesterol in patients with primary hypercholesterolemia, heterozygous familial and non-familial hypercholesterolemia and type II mixed (mixed) hyperlipidemia;

in combination with a diet for the treatment of patients with high serum triglycerides (type IV according to Fredrickson) and patients with dysbetalipoproteinemia (type III according to Fredrickson), in whom diet therapy does not give an adequate effect;

to reduce the concentration of total cholesterol and cholesterol / LDL in patients with homozygous familial hypercholesterolemia, when diet therapy and other non-pharmacological treatments are not effective enough.

Dosage regimen

Before prescribing the drug Atorvastatin, the patient should recommend a standard lipid-lowering diet, which he must continue to adhere to throughout the entire period of therapy. The drug is taken orally, at any time of the day with food or regardless of the meal time. The dose is selected taking into account the initial levels of cholesterol / LDL, the purpose of therapy and the individual effect. The initial dose is on average 10 mg 1 time / day. The dose varies from 10 to 80 mg 1 time / day. At the beginning of treatment and / or during an increase in the dose of Atorvastatin, it is necessary to monitor the plasma lipid content every 2-4 weeks and adjust the dose accordingly. With primary hypercholesterolemia and mixed hyperlipidemia, as well as type III and IV hyperlipidemia according to Fredrickson, in most cases it is sufficient to prescribe a drug at a dose of 10 mg 1 time / day. A significant therapeutic effect is observed, as a rule, after 2 weeks; maximum therapeutic effect is usually observed after 4 weeks. With prolonged treatment, this effect persists. With homozygous familial hypercholesterolemia, the drug is prescribed at a dose of 80 mg (4 tablets, 20 mg each) 1 time / day. The use of the drug in patients with renal failure and kidney disease does not affect the level of atorvastatin in the blood plasma or the degree of decrease in cholesterol / LDL when it is used, therefore, changing the dose of the drug is not required. With liver failure, the dose must be reduced. When using the drug in elderly patients, there were no differences in safety, efficacy, or achievement of the goals of lipid-lowering therapy in comparison with the general population.

Side effect

From the side of the nervous system: more often 2% - insomnia, dizziness; less often 2% - headache, asthenia, malaise, drowsiness, nightmares, paresthesias, peripheral neuropathy, amnesia, emotional lability, ataxia, facial paralysis, hyperkinesia, migraine, depression, hypesthesia, loss of consciousness.

From the sensory organs: less than 2% - amblyopia, tinnitus, dry conjunctiva, disturbed accommodation, hemorrhage in the retina, deafness, glaucoma, parosmia, loss of taste, perversion of taste.

From the cardiovascular system: more often 2% - chest pain; less often 2% - palpitations, vasodilation symptoms, orthostatic hypotension, increased blood pressure, phlebitis, arrhythmia, angina pectoris.

From the hemopoietic system: less than 2% - anemia, lymphadenopathy, thrombocytopenia.

From the respiratory system: more often 2% - bronchitis, rhinitis; less often 2% - pneumonia, dyspnea, exacerbation of bronchial asthma, nosebleeds.

From the digestive system: more often 2% - nausea; less than 2% - heartburn, constipation or diarrhea, flatulence, gastralgia, abdominal pain, decreased or increased appetite, dry mouth, belching, dysphagia, vomiting, stomatitis, esophagitis, glossitis, erosive and ulcerative lesions of the oral mucosa, gastroenteritis, hepatitis, biliary colic, cheilitis, duodenal ulcer, pancreatitis, cholestatic jaundice, impaired liver function, rectal bleeding, melena, bleeding gums, tenesmus.

From the musculoskeletal system: often 2% - arthritis; less often 2% - leg muscle cramps, bursitis, tendosynovitis, myositis, myopathy, arthralgia, myalgia, rhabdomyolysis, torticollis, muscle hypertonicity, joint contractures.

From the urinary system: often 2% - peripheral edema; less often 2% - dysuria (including pollakiuria, nocturia, urinary incontinence or urinary retention, imperative urination, nephritis, hematuria, nephrourolithiasis.

From the genitals and mammary gland: more often 2% - urogenital infections; less often 2% - vaginal bleeding, metrorrhagia, epididymitis, decreased libido, impotence, impaired ejaculation, gynecomastia, mastodynia.

On the part of the skin and subcutaneous tissues: more often 2% - alopecia, xeroderma, increased sweating, eczema, seborrhea, ecchymosis, petechiae.

Allergic reactions: less than 2% - itching, skin rash, contact dermatitis "rarely - urticaria, angioedema, facial edema, photosensitivity, anaphylaxis, erythema multiforme exudative (including Stevens-Johnson syndrome), toxic epidermal necrolysis (syndrome Lyella).

On the part of laboratory indicators: less than 2% - hyperglycemia, hypoglycemia, increased serum CPK, albuminuria.

Other: less than 2% - an increase in body weight, exacerbation of gout.

Contraindications

  • active liver diseases or an increase in the activity of liver enzymes of unknown origin (more than 3 times compared with VGN);
  • liver failure (severity according to the classification of Child-Pugh A and B);
  • pregnancy;
  • lactation period;
  • age up to 18 years (effectiveness and safety have not been established);
  • hypersensitivity to the components of the drug.

  • With caution, the drug should be prescribed for alcohol abuse, a history of liver diseases, severe electrolyte imbalance, endocrine and metabolic disorders, arterial hypotension, severe acute infections (sepsis), uncontrolled epilepsy, extensive surgical interventions, injuries, and skeletal muscle diseases.

    Pregnancy and lactation

    Atorvastatin is contraindicated in pregnancy and lactation (breastfeeding). It is not known whether atorvastatin is excreted in breast milk. Given the possibility of adverse events in infants, if necessary, use of the drug during lactation should decide on the termination of breastfeeding. Women of reproductive age should use adequate methods of contraception during treatment. Atorvastatin can be prescribed to women of reproductive age only if the probability of pregnancy is very low, and the patient is informed about the possible risk to the fetus during therapy.

    Special instructions

    Before starting treatment with Atorvastatin, the patient must be prescribed a standard hypocholesterol diet, which he must follow during the entire treatment period. The use of inhibitors of HMG-CoA reductase to reduce the concentration of lipids in the blood can lead to a change in biochemical parameters reflecting liver function. Liver function should be monitored before the start of therapy, 6 weeks, 12 weeks after the start of the use of the drug Atorvastatin and after each dose increase, and also periodically, for example, every 6 months. An increase in the activity of hepatic enzymes in blood serum can be observed during therapy with Atorvastatin.Patients who have an increase in enzyme activity should be monitored until the indicators return to normal values. In the event that the ALT or ACT values ​​are more than 3 times higher than VGN, it is recommended to reduce the dose of Atorvastatin or stop 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. Atorvastatin treatment can cause myopathy. The diagnosis of myopathy (muscle pain and weakness in combination with an increase in CPK activity by more than 10 times compared with VGN) should be discussed in patients with common 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 CPK activity or if there is a confirmed or suspected myopathy. The risk of myopathy in the treatment of other drugs of this class increased with the simultaneous use of cyclosporine, fibrates, erythromycin, nicotinic acid or antifungal agents from the azole group.Many of these drugs inhibit CYP3A4-mediated metabolism and / or drug transport. Atorvastatin is biotransformed under the influence of CYP3A4. Prescribing atorvastatin in combination with fibrates, erythromycin, immunosuppressive agents, antifungal agents from the azole group or nicotinic acid in hypolipidemic doses, the expected benefit and risk of treatment should be carefully weighed and patients should be regularly observed to detect muscle pain or weakness, especially during the first months of treatment and during periods of increasing doses of any drug. In such situations, a periodic determination of KFK activity can be recommended, although such control does not prevent the development of severe myopathy. When using the drug Atorvastatin, as well as other drugs of this class, cases of rhabdomyolysis with acute renal failure due to myoglobinuria are described. Atorvastatin therapy should be temporarily discontinued or completely discontinued if there are signs of possible myopathy or there are risk factors for the development of renal failure due to rhabdomyolysis (for example, severe acute infection, arterial hypotension, serious surgery, trauma, severe metabolic, endocrine and electrolyte disturbances 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 patients with obesity and treatment of other conditions. Patients should be warned that they should immediately consult a doctor if unexplained pain or muscle weakness occurs, especially if they are accompanied by malaise or fever.Influence on the ability to drive vehicles and control mechanisms. The adverse effect of the drug Atorvastatin on the ability to drive a car and work with mechanisms was not reported.

    Overdose

    Treatment: there is no specific antidote; symptomatic therapy is indicated. Hemodialysis is ineffective.