Atorvastatin tablets p/o 40mg №10×3

Name:
Atorvastatin tablets 40 mg in a cell. pack No. 10×3
Description:
Film-coated tablets are white, round, with a biconvex surface. Composition One tablet contains: active ingredient: atorvastatin ? 10 mg, 20 mg and 40 mg; excipients: lactose monohydrate, microcrystalline cellulose, crospovidone (type A), hypromellose (methocel E6 type 2910), polysorbate 80, sodium lauryl sulfate, magnesium stearate, calcium carbonate, opadry 85 F (polyvinyl alcohol, partially hydrolyzed; macrogol 3350; talc; titanium dioxide E171). Pharmacotherapeutic group Hypolipidemic agent. HMG-CoA reductase inhibitors. ATX code: C10AA05. Pharmacological propertiesPharmacodynamics Atorvastatin belongs to a group of medicines, the main action of which is to reduce the level of total cholesterol and LDL cholesterol (low density lipoprotein) in the blood. The drug also lowers triglyceride levels and raises HDL (high density lipoprotein) cholesterol levels in the blood. The mechanism of action of atorvastatin is mainly to inhibit the activity of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A-(HMG-CoA-) reductase, which catalyzes the conversion of HMG-CoA to mevalonic acid. This transformation is one of the early stages in the chain of cholesterol synthesis in the body. Suppression of cholesterol synthesis by atorvastatin leads to increased reactivity of LDL receptors in the liver, as well as in extrahepatic tissues. These receptors bind LDL particles and remove them from the blood plasma, which leads to a decrease in blood cholesterol levels. Since atorvastatin also inhibits the secretion of very-low-density lipoprotein cholesterol in the liver, this seems to be the mechanism for lowering triglyceride levels, as their binding to the ApoB carrier protein is weakened and, thereby, their plasma clearance is increased. The mechanism by which atorvastatin increases HDL cholesterol levels remains unclear. In addition to affecting plasma lipid levels, atorvastatin also has a number of other effects that are part of its anti-atherogenic potential. Among other things, atorvastatin inhibits the synthesis of isoprenoids, which are growth factors for smooth muscle cells of the inner lining of blood vessels. Atorvastatin reduces plasma viscosity and the activity of some coagulation and aggregation factors. It thus improves hemodynamics and contributes to a favorable balance of blood coagulation. HMG-CoA reductase inhibitors also affect macrophage metabolism and thereby inhibit macrophage activation and atherosclerotic plaque rupture. Pharmacokinetics As part of the drug, atorvastatin is present in its active form – in the form of a calcium salt. Atorvastatin is approximately 80% absorbed from the gastrointestinal tract. Absorption occurs quickly (tmax = 1-2 hours). Although food intake reduces the level of absorption, this does not affect the effectiveness of atorvastatin. Due to extensive first-pass metabolism and first pass clearance in the gastrointestinal mucosa, atorvastatin has a bioavailability of only 12%. The mean volume of distribution (Vd) of atorvastatin is 381 liters. More than 98% of atorvastatin binds to plasma proteins. Atorvastatin does not cross the blood-brain barrier. In the liver, it is metabolized with the participation of the cytochrome P-450 3A4 isoenzyme to ortho- and parahydroxylated derivatives, as well as various beta-oxidation metabolites. Approximately 70% of the inhibitory activity against HMG-CoA reductase is attributed to these active metabolites of atorvastatin. The half-life (t1 / 2) is on average 14 hours; the half-life of the inhibitory activity for the target enzyme is 20-30 hours. Approximately 46% of atorvastatin is excreted in the faeces and less than 2% is excreted in the urine. Differences in pharmacokinetics depending on the age or sex of the patient are not too significant to require dose adjustment. As a rule, the effect of Atorvastatin appears 2 weeks after the start of use, and the maximum effectiveness is achieved 4 weeks after the start of treatment. Patients with impaired renal function Renal disease does not affect plasma concentrations of atorvastatin and its active metabolites or their effect on lipid metabolism. Therefore, dose adjustment in patients with renal dysfunction is not required. Patients with impaired liver function Plasma concentrations of atorvastatin increased markedly in patients with chronic alcoholic liver disease. Cmax and AUC were 4 times greater in patients with Child-da-Pugh grade A hepatic impairment and approximately 16 times and 11 times higher, respectively, in patients with grade B. Elderly patients Plasma atorvastatin concentrations were higher (approximately 40% for Cmax and 30% for AUC) in healthy older people (age >65 years) than in young people. Clinical evidence suggests a greater reduction in LDL-C at any dose in the elderly patient population than in younger adults. Children In an open 8-week study, pediatric patients of Tanner stage I (n=15) and ? II stage of sexual development according to Tanner (n=24) at the age of 6-17 years with heterozygous hereditary hypercholesterolemia and initial level of HDL-C ? 4 mmol/l received atorvastatia, respectively, 5 or 10 mg in chewable tablets, or 10 and 20 mg in coated tablets, 1 time per day. In a population model of the pharmacokinetics of atorvastatin, body weight was the only significant covariate. The apparent clearance of atorvastatin after oral administration in pediatric patients was similar to that in adults with allometric scaling of data by body weight. In the exposure range of atorvastatin and o-hydroxyatorvastatin, there was a steady decrease in the levels of HDL-C and total cholesterol. Gender Plasma concentrations of atorvastatin in women differed from those in men (approximately 20% higher for Cmax and 10% lower for AUC); however, there was no clinically significant difference in LDL-C reduction with atorvastatin between males and females. SLC01B1 polymorphism The entry into the liver of all inhibitors of HMG-CoA reductase, including atorvastatia, occurs, among other things, with the participation of the OATP1B1 transport protein. In patients with polymorphisms in the SLC01B1 gene, there is a risk of increased exposure to atorvastatin, which may lead to an increased risk of rhabdomyolysis (see the “Precautions” section). Nucleotide polymorphism in the gene encoding OATP1B1 (SLCO1B1 C.521CC), compared with people without this genotype variant (c.521TT), was associated with a 2.4-fold increase in atorvastatin AUC. In addition, these patients may have a genetically determined violation of the delivery of atorvastatin to the liver. The effect on the efficacy of atorvastatin is unknown. Preclinical Safety Data Atorvastatin has shown negative results in both in vitro and in vivo mutagenicity studies. Atorvastatin has not been found to be carcinogenic in rats, but high doses in mice have resulted in the development of hepatocellular adenomas in males and hepatocellular carcinomas in females, approximately 6-11 times the AUC0-24h in humans after the highest recommended dose. There is evidence from experimental animal studies that inhibitors of HMG-CoA reductase may affect the development of the embryo or fetus. In rats, rabbits and dogs, atorvastatin had no effect on fertility and was not teratogenic, however, maternally toxic doses were observed to cause fetal toxicity in rats and rabbits. There was a delay in fetal development of the offspring, and postnatal survival decreased when exposed to high doses of atorvastatin in females. The rats had evidence of placental abruption. In rats, plasma concentrations of atorvastatin are similar to those in milk. In male rats, doses of atorvastatin up to 225 mg/kg (56 times greater than in humans) did not adversely affect fertility. Studies in male rats at doses up to 175 mg/kg (15 times the human exposure) did not result in changes in fertility. In the epididymis, 2 of 10 rats treated with 100 mg/kg/day atorvastatin for 3 months developed aplasia and aspermia (16-fold human AUC at 80 mg); testicular weight was significantly lower at the 30 and 100 mg/kg doses, and epididymis was lower at the 100 mg/kg dose. In male rats dosed at 100 mg/kg/day for 11 weeks prior to mating, sperm motility, sperm head concentration decreased, and sperm abnormalities increased. Atorvastatia did not adversely affect sperm parameters or reproductive organ histopathology in dogs at doses of 10, 40, or 120 mg/kg over several years. Indications for use Hypercholesterolemia Atorvastatin is indicated as an adjunct to diet for the treatment of patients with elevated levels of total cholesterol, LDL (low density lipoprotein), apolyprotein B and triglycerides, and to increase HDL (high density lipoprotein) cholesterol in adult patients with primary hypercholesterolemia (hereditary heterozygous and non-hereditary hypercholesterolemia), combined (mixed) hyperlipidemia (Fredrickson type IIa and IIb), elevated plasma triglycerides (Fredrickson type IV), primary dysbetalipoproteinemia (Friedrickson type III), in cases where diet and other non-pharmacological measures do not provide sufficient effect. Atorvastatin is also indicated for lowering total and LDL cholesterol in patients with homozygous familial hypercholesterolemia, in addition to other lipid-lowering measures (eg, LDL apheresis), or when such treatment options are not available. Prevention of cardiovascular disease in adults In adults without clinical evidence of cardiovascular disease but with multiple risk factors for coronary heart disease such as age, smoking, hypertension, low HDL-C (X-HDL), or early coronary disease heart disease in a family history, Atorvastatin is indicated for: reducing the risk of myocardial infarction; reducing the risk of stroke; reducing the risk of undergoing revascularization surgery and the risk of developing angina pectoris. In adult patients with type 2 diabetes and without symptomatic coronary heart disease, but with multiple factors in the development of coronary artery disease, such as retinopathy, albuminuria, smoking or hypertension, Atorvastatin is indicated to: reduce the risk of myocardial infarction; reduce the risk of stroke. In adult patients with clinically significant cardiovascular disease, the use of atorvastatin is indicated to: heart attack; reduced risk of fatal and non-fatal stroke; reduced risk of undergoing revascularization surgery; reduced risk of hospitalization for CHF; reduced risk of angina pectoris. Use in children (patients aged 10-17 years) , LDL cholesterol (low-density lipoprotein), apolipoprotein B in girls after menarche and in boys aged 10-17 years with a history of heterozygous hereditary hypercholesterolemia, if after an appropriate trial therapeutic diet, the following indicators are present: a. cholesterol level – LDL remains ? 190 mg/dL or b. cholesterol level – LDL remains ? 160 mg/dL and: * have a family history of early cardiovascular disease, or * the children currently have 2 or more other risk factors for cardiovascular disease. Contraindications hypersensitivity to the active substance or to any of the auxiliary components of the drug; liver disease in the active stage; persistent elevated serum transaminases of unknown origin more than 3 times the upper limit of the norm; skeletal muscle diseases; pregnancy and lactation; women of reproductive age, not using appropriate contraceptive measures. Dosage and administration Before starting treatment with Atorvastatin, the patient must be transferred to a diet that reduces blood lipids, which must be observed during drug therapy. The recommended starting dose is 10 mg daily. Depending on the desired effect, the daily dose may be increased to no more than 80 mg. The patient should take Atorvastatin once at any time of the day, but at the same time each day. The drug is taken regardless of the meal. A significant therapeutic effect is noted after two weeks of treatment, and the maximum effect develops after four weeks. Therefore, the dose should not be changed earlier than four weeks after the start of the drug in the previous dose. Primary hypercholesterolemia and combined (mixed) hyperlipidemia Treatment begins with the recommended initial dose, which, depending on the effect, is increased after four weeks of treatment with the initially selected dose. The maximum daily dose is 80 mg. Heterozygous familial hypercholesterolemia The initial dose is 10 mg per day. Dose titration should be carried out individually at 4-week intervals up to a dose of 40 mg per day. Thereafter, the dose can either be increased to 80 mg daily or combined treatment with atorvastatin 40 mg once daily with bile acid sequestrants can be used. Homozygous familial hypercholesterolemia Adult patients. The dosage 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 was observed when using the drug in a daily dose of 80 mg. Atorvastatin is used as an add-on therapy to other treatments (plasmapheresis) or as the main treatment if therapy with other methods is not possible. In the elderly and in patients with renal insufficiency, it is not necessary to change the recommended doses of Atorvastatin. In patients with impaired liver function, caution is necessary due to the slowdown in the excretion of the drug from the body. In such a situation, clinical and laboratory parameters should be carefully monitored, and if significant pathological changes are detected, the dose should be reduced, or treatment should be discontinued. Pediatric use Hypercholesterolemia Use in children should only be carried out by physicians with experience in this field. To achieve the effect, it is recommended to regularly re-examine patients. In patients with heterozygous familial hypercholesterolemia 10 years of age or older, the recommended starting dose is 10 mg atorvastatin daily. The dose may be increased up to 80 mg per day, taking into account the individual response to treatment and tolerability. The dose should be selected individually in accordance with the purpose of therapy. Adjustments are made at intervals of at least 4 weeks. Dose titration up to 80 mg per day is based on data obtained in studies in adults and limited clinical studies in children with heterozygous familial hypercholesterolemia. There are limited data on safety and efficacy in children with heterozygous familial hypercholesterolemia 6 to 10 years of age. Atorvastatin is not indicated for the treatment of children under 10 years of age. Combination lipid-lowering therapy Atorvastatin can be used in conjunction with bile acid sequestrants. The combination of HMG-CoA reductase inhibitors (statins) and fibrates should be used with caution (see sections “Precautions” and “Interaction with other medicinal products and other forms of interaction”). Dosing in patients receiving cyclosporine, clarithromycin, itraconazole, or certain protease inhibitors Atorvastatin therapy should be avoided when treated with cyclosporine, HIV protease inhibitors (tipranavir plus ritonavir), or hepatitis C virus protease inhibitors (telaprevir). In patients with HIV infection receiving lopinavir plus ritonavir, caution should be exercised when prescribing atorvastatin and the lowest dose should be used. In patients receiving clarithromycin, itraconazole, or in patients with HIV receiving the combination of saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, or fosamprenavir plus ritonavir, atorvastatin therapy should be limited to 20 mg with appropriate clinical supervision to ensure that the lowest necessary dose is used. dose. In patients receiving the HIV protease inhibitor nelfinavir, the hepatitis C protease inhibitor boceprevir, atorvastatin therapy should be limited to a dose of 40 mg with appropriate clinical supervision to ensure that the lowest necessary dose is used (see sections “Precautions” and “Interaction with other drugs and other forms of interaction”). Side effects Information on adverse reactions is presented in accordance with the system-organ classification and frequency of occurrence. Frequency categories were determined according to the following classification: very often (?1/10), often (?1/100, but <1/10), infrequently (?1/1000, but <1/100), rare (?1 /10,000 but <1/1,000), very rare (<1/10,000), frequency unknown (cannot be estimated from available data). Infections and invasions: often: nasopharyngitis. Blood and lymphatic system disorders: Uncommon: Thrombocytopenia. Immune system disorders: often: allergic reactions; very rarely: anaphylaxis. Metabolic and nutritional disorders: infrequently: anorexia. Mental disorders: infrequently: amnesia, nightmares, insomnia. Nervous system disorders: often: headache, insomnia, dizziness, paresthesia; infrequently: peripheral neuropathy, drowsiness, hypesthesia, taste disturbances. Respiratory, thoracic and mediastinal disorders Common: chest pain, pain in the pharynx and larynx, epistaxis. On the part of the organ of vision: infrequently: blurred vision; rarely: visual disturbances. On the part of the organ of hearing and labyrinth: infrequently: ringing in the ears; very rare: hearing loss. Liver and biliary tract disorders: rarely: hepatitis, cholestasis; very rarely: liver failure. Gastrointestinal disorders: often: nausea, flatulence, dyspepsia, constipation, diarrhea, infrequently: vomiting, pancreatitis, infrequently: pain in the upper and lower abdomen, belching. Skin and subcutaneous tissue disorders Common: skin rash, pruritus Uncommon: urticaria Very rare: angioedema, alopecia, bullous rash (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis). Muscular, skeletal and connective tissue disorders: often: myalgia, arthralgia, back pain, pain in the extremities, muscle spasms, swelling of the joints; infrequently: myopathy, neck pain, muscle weakness; rarely: myositis, rhabdomyolysis, tendinopathy (sometimes complicated by tendon rupture); frequency not known: necrotizing autoimmune myopathy. Reproductive system and breast disorders: very rare: gynecomastia. General disorders and reactions at the injection site: often: asthenia, peripheral edema; infrequently: malaise, weight gain, chest pain, fever. Laboratory and instrumental data: often: elevated levels of creatinine kinase (CK) in the blood; infrequently: elevated levels of serum transaminases (ALT, AST), a positive test result for the content of leukocytes in the urine; very rarely: hyperglycemia, hypoglycemia. For some adverse reactions classified as "very rare", a causal relationship with the drug has not been established. Serum transaminase levels are dose dependent and are reversible in all patients. CC levels exceeding the normal upper limit by 10 times were found in 0.4% of patients; 0.1% of whom felt muscle pain or weakness. In the event of serious adverse reactions, treatment should be discontinued. Children and adolescents Children and adolescents aged 10 to 17 years who were treated with atorvastatin had an adverse effect profile generally similar to that of patients treated with placebo. The most common side effects, regardless of the assessment of their causal relationship in both groups, were infections. During a three-year study, there was no clinically significant effect on physical and sexual development as measured by the Tanner scale and measures of height and body weight. The safety profile in children and adolescents was largely consistent with the known safety profile of atorvastatin in adults. The Clinical Safety Database contains information on 520 pediatric patients treated with atorvastatin. Of these, 7 patients were under 6 years of age, 121 patients were 6 to 9 years of age, and 392 patients were 10 to 17 years of age. According to available data, the frequency, type and severity of side effects in children are similar to those in adults. The following side effects have also been reported with some statins: sexual dysfunction; depression; in rare cases, interstitial lung disease, especially in the case of long-term therapy (see the Precautions section); diabetes mellitus: the frequency depends on the presence or absence of risk factors (fasting blood glucose >5.6 mmol/l, BMI>30 kg/m?, elevated triglycerides, presence of arterial hypertension). the benefit-risk ratio of the medicinal product. Health care professionals are encouraged to report any suspected adverse drug reactions through national adverse drug reaction and drug failure reporting systems. Precautions Atorvastatin should be used with caution in patients who abuse alcohol, as well as those with a history of liver disease. Treatment with Atorvastatin may lead to an increase in the activity of “liver” enzymes in the serum. This increase is usually small and has no clinical significance; however, it is recommended to determine the activity of “liver” enzymes in the blood serum before starting treatment, and then regularly monitor their activity during treatment. If there is more than a threefold increase in AST and / or ALT activity compared to the upper limit of the normal range, then treatment with Atorvastatin should be discontinued. The SPARCL (Stroke Prevention by Aggressively Lowering Cholesterol) study showed that in a retrospective analysis of stroke subtypes in non-CAD patients with a recent stroke or transient ischemic attack (TIA) who started atorvastatin 80 mg, there was an increased increase in the frequency of hemorrhagic strokes compared with the placebo group. The increased risk was especially pronounced in patients with a history of hemorrhagic stroke or lacunar infarction. For patients with hemorrhagic stroke or lacunar infarction, the risk-benefit ratio for an atorvastatin 80 mg dose is uncertain, and the potential risk of hemorrhagic stroke should be carefully assessed prior to initiating treatment. Treatment with Atorvastatin can cause myalgia, myositis, and myopathy, which can lead to rhabdomyolysis, a potentially life-threatening condition characterized by an increase in serum creatine kinase (> 10 times the upper limit of normal), myoglobinemia, and myoglobinuria with possible development of renal failure. In very rare cases, necrotizing autoimmune myopathy (IMNM) has been reported during or after treatment with some statins. The clinical features of IMNM are persistent proximal muscle weakness and elevated serum creatine kinase levels that persist despite discontinuation of statin treatment. Atorvastatin should be used with caution in patients predisposed to rhabdomyolysis. Before initiating statin therapy, creatine kinase levels should be assessed if the following risk factors or diseases are present: impaired renal function, hypothyroidism, personal or family history of hereditary myopathies, history of muscle toxicity associated with the administration of a statin or fibrate, liver disease and / or significant history of alcohol consumption, elderly patients (> 70 years). In this case, it is necessary to take into account the existence of other predisposing factors for the occurrence of rhabdomyolysis and circumstances in which an increase in plasma cretinkinase levels can be observed, such as interaction (see section “Interaction with other drugs means and other forms of interaction”) and specific patient groups, including genetic subpopulations. In such situations, a careful risk-benefit analysis is required, and close clinical monitoring should be ensured. If creatine kinase levels are significantly elevated (more than 5 times the upper limit of normal) prior to treatment, then therapy should not be started. The risk of rhabdomyolysis is increased when atorvastatin is used concomitantly with certain other medicinal products that increase plasma concentrations of atorvastatin, such as strong inhibitors of CYP3A4 or transport proteins (eg, cyclosporine, telithromycin, clarithromycin, delavirdine, styripentol, ketoconazole, voriconazole, itraconazole, posaconazole and some HIV protease inhibitors including ritonavir, lopinavir, atazanavir, indinavir, darunavir, etc.). In addition, the risk of myopathy is increased with concomitant use of gemfibrozil and other fibrates, boceprevir, erythromycin, niacin, ezetimibe, telaprevir, or the tipranavir/ritonavir combination. If possible, alternative medicinal products that do not interact with atorvastatin should be considered instead. In cases where the concomitant use of these medicinal products with atorvastatin is unavoidable, the benefit and risk and the balance between them must be considered. In patients receiving medicinal products that increase plasma concentrations of atorvastatin, the lowest necessary maximum dose of atorvastatin should be used. For strong inhibitors of CYP3A4, it is necessary to additionally reduce the initial dose of atorvastatin and carry out clinical monitoring of patients (see the section “Interaction with other medicinal products and other forms of interaction”). Atorvastatin should not be co-administered with systemic fusidic acid preparations, even within 7 days after discontinuation of fusidic acid therapy. If systemic administration of fusidic acid is mandatory for patients, statin therapy is excluded throughout the entire period of treatment. Rhabdomyolysis has been reported in patients taking fusidic acid and statins in combination (including some cases with a fatal outcome (see the section “Interaction with other medicinal products and other forms of interaction”). Patients should immediately consult a doctor if they notice any or signs of muscle weakness, pain, or impaired sensation Statin therapy may be resumed 7 days after the last dose of fusidic acid If, in exceptional cases, long-term systemic administration of fusidic acid is necessary, such as, for example, for the treatment of severe infections, the concomitant use of atorvastatin with fusidic acid is recommended should be considered individually and under close medical monitoring.Treatment with atorvastatin should be temporarily suspended in any patient with an acute, serious condition causing myopathy or a risk factor predisposing to the development of renal failure secondary to rhabdomyolysis (eg, acute infection, hypotension, major surgery, trauma, severe metabolic, endocrine, and electrolyte disturbances, and uncontrolled seizures). Endocrine function Statins interfere with cholesterol synthesis and could theoretically interfere with steroid synthesis in the adrenal glands and/or gonads. Clinical studies have shown that atorvastatin does not cause changes in basal plasma cortisol concentrations or disturbances in adrenal reserve. The effect of statins on male fertility has not been studied in sufficient numbers of patients. Effects, if any, on the pituitary-gonadal axis in premenopausal women are unknown. Caution should be exercised if the statin is used concomitantly with medicinal products that may decrease the level or activity of endogenous steroid hormones, such as ketoconazole, spironolactone, and cimetidine. CNS toxicity One female dog treated for 3 months at 120 mg/kg/day developed a cerebral hemorrhage. Another dog, which was euthanized after 11 weeks of dose escalation to 280 mg/kg/day, experienced cerebral hemorrhage and optic nerve vacuolization. A dose of 120 mg/kg resulted in approximately 16-fold systemic exposure compared to the area under the curve (AUC, 0-24 hours) derived from a maximum human dose of 80 mg per day. A single tonic spasm was observed in each of two male dogs (one at 10 mg/kg/day and one at 120 mg/kg/day) in a two-year study. No CNS lesions were observed in mice after chronic treatment up to 2 years with doses up to 400 mg/kg/day or in rats treated with doses up to 100 mg/kg/day. These doses were 6 to 11 times (mouse) and 8 to 16 times (rat) compared to the AUC (0-24) based on the maximum recommended human dose of 80 mg/day. In dogs treated with other statins, damage to the vessels of the central nervous system was observed, characterized by perivascular hemorrhages, edema, and mononuclear cell infiltration of the perivascular spaces. Drugs in this class caused optic nerve degeneration (retinogenic tissue degeneration) in clinically healthy dogs in a dose-dependent manner at a dose that produced drug concentrations 30 times higher than the average drug level in humans at the highest recommended doses. Creatine Kinase Level Determination Creatine kinase should not be measured after strenuous exercise or exposure to other possible factors that cause an increase in creatine kinase levels, as this will make readings more difficult to interpret. If the values of creatine kinase are significantly increased (more than 5 times the upper limit of normal) before starting treatment, then after 5-7 days it is necessary to retest. Monitoring During Therapy Patients should be promptly informed of pain, cramps, or skeletal muscle weakness, especially if associated with general malaise or fever. If such symptoms occur during treatment with atorvastatin, creatine kinase activity should be measured. If the level of creatine kinase is significantly elevated (more than 5 times the upper limit of normal), then therapy should be discontinued. In the case of persistent and severe muscle symptoms, therapy should be discontinued, even if creatine kinase values are not significantly increased (5 times and less than the upper limit of normal). When symptoms resolve and creatine kinase levels return to normal, restarting treatment with atorvastatin at the lowest dose or another statin regimen may be considered after careful monitoring. Treatment with atorvastatin should be discontinued if serum clinically significant levels of creatine kinase (greater than 10 times the upper limit of normal) are present in the blood or if rhabdomyolysis is diagnosed or suspected. Complaints that may occur in patients: shortness of breath, non-productive cough and general health disorders (fatigue, weight loss and fever). If there is a suspicion that the patient has developed interstitial lung disease, statin therapy should be discontinued. Diabetes mellitus There is evidence that statins, as a class of substances, increase blood sugar levels and in some patients at high risk of developing diabetes mellitus can cause hyperglycemia, requiring adequate treatment. However, this risk is offset by a reduction in vascular risk and therefore should not lead to discontinuation of statin treatment. As recommended, patients at high risk (fasting blood glucose 5.6 to 6.9 mmol/L, BMI >30 kg/m2, elevated triglycerides, hypertension) should be closely monitored clinically and laboratory parameters . The medicinal product contains lactose. This medicinal product is not suitable for patients with rare hereditary problems of galactose intolerance, lactase enzyme deficiency or glucose-galactose malabsorption syndrome. Fertility, pregnancy and lactation Women of childbearing potential Women of childbearing potential should use appropriate contraception during treatment. Pregnancy Atorvastatin is contraindicated during pregnancy. Safety during pregnancy has not yet been proven. There have been no controlled clinical trials of atorvastatin in pregnant women. There are rare reports of congenital anomalies following intrauterine exposure to MMC-CoA reductase inhibitors. Animal studies have shown reproductive toxicity. Treatment of the mother with atorvastatin may reduce the concentration of mevalonate, a cholesterol biosynthetic precursor, in the fetus. Generally, discontinuation of lipid-lowering therapy during pregnancy has little effect on the long-term risk of developing primary hypercholesterolemia. Therefore, Atorvastatin should not be used by pregnant women, women who think they may be pregnant or think they are pregnant. Treatment with Atorvastatin should be discontinued during pregnancy or until no pregnancy is known. Lactation It is not known whether atorvastatin or its metabolites pass into breast milk. When studied in rats, similar levels of atorvastatin and its active metabolites were obtained in both milk and plasma. Because of the potential for serious side effects, women taking Atorvastatin should not breastfeed. Atorvastatin is contraindicated in breastfeeding. Reproductive function In animal studies, atorvastatin did not affect the reproductive function of males or females. Influence on the ability to drive vehicles and work with mechanisms Atorvastatin does not affect the ability to drive vehicles and work with mechanisms. Overdose There are no specific treatments for overdos