Atorvastatin-SZ, 40 mg 30 pcs
€7.68 €6.72
Atorvastatin is a selective competitive inhibitor of HMG-CoA reductase, a key enzyme converting 3-hydroxy-3-methylglutaryl-CoA to mevalonate, a precursor of steroids, including cholesterol; a synthetic hypolipidemic drug.
. In patients with homozygous and heterozygous familial hypercholesterolemia, nonfamilial forms of hypercholesterolemia and mixed dyslipidemia, atorvastatin reduces plasma cholesterol (CH) low density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apo-B), as well as very low density lipoprotein cholesterol (VLDL-C) and triglycerides (TG), causes unstable increase of high density lipoprotein cholesterol (HDL-C) concentration.
Atorvastatin reduces plasma concentrations of cholesterol and lipoproteins by inhibiting HMG-CoA reductase and cholesterol synthesis in the liver and increasing the number of “hepatic” LDL receptors on the cell surface, which leads to increased capture and catabolism of LDL-C.
Atorvastatin decreases formation of LDL-C and the number of LDL particles, causes a pronounced and sustained increase in LDL receptor activity in combination with favorable qualitative changes of LDL particles and decreases LDL-C concentration in patients with homozygous hereditary familial hypercholesterolemia resistant to therapy with other hypolipidemic agents.
Atorvastatin at doses of 10 mg to 80 mg reduces cholesterol concentration by 30% to 46%, LDL-C by 41% to 61%, apolipoprotein-b by 34% to 50% and TG by 14% to 33%. The results of therapy are similar in patients with heterozygous familial hypercholesterolemia, nonfamilial forms of hypercholesterolemia and mixed hyperlipidemia, including patients with type 2 diabetes.
In patients with isolated hypertriglyceridemia atorvastatin reduces cholesterol, LDL-C, LDL-C, apo-B and TG concentrations and increases HDL-C concentration. In patients with dysbetalipoproteinemia, atorvastatin reduces the concentration of intermediate-density lipoprotein cholesterol.
In patients with hyperlipoproteinemia of type IIa and IIb according to Fredrickson classification mean increase of HDL-C concentration during treatment with atorvastatin (10-80 mg) in comparison with baseline is 5.1 % – 8.7 % and it is not dose dependent. There is a significant dose-dependent decrease in the values of the ratios: total cholesterol/CHD-LDP and CHD-LDL/CHD-LDP by 29 % – 44 % and 37 % – 55 %, respectively.
The antisclerotic effect of atorvastatin is a consequence of its effect on the vascular wall and blood components. Atorvastatin inhibits the synthesis of isoprenoids, which are growth factors of the cells of the inner membrane of blood vessels. Under the action of atorvastatin endothelium-dependent dilation of blood vessels improves, concentration of HDL-C, apolipoprotein B, TG decreases, concentration of HDL-C and apolipoprotein A cholesterol increases.
Atorvastatin reduces plasma viscosity and the activity of some clotting factors and platelet aggregation. Due to this it improves hemodynamics and normalizes the state of the clotting system. HMG-CoA reductase inhibitors also affect the metabolism of macrophages, block their activation and prevent the rupture of atherosclerotic plaque.
Atorvastatin-CZ at a dose of 80 mg significantly reduces the risk of coronary complications and mortality rate by 16% after a 16-week course, and the risk of readmission for angina with signs of myocardial ischemia by 26%. In patients with different baseline concentrations of LDL-C, Atorvastatin-CS causes reduction of risk of ischemic complications and mortality (in patients with myocardial infarction without Q-wave and unstable angina, as well as in men and women, and in patients aged younger and older than 65 years).
The decrease in plasma concentration of LDL-C correlates better with the drug dose than with its plasma concentration. The dose is adjusted taking into account the therapeutic effect (see section “Dosage and administration”).
Therapeutic effect is achieved 2 weeks after the start of therapy, reaches a maximum after 4 weeks and lasts for the duration of therapy.
Pharmacokinetics:
Intake
Atorvastatin is quickly absorbed after oral administration: time of reaching its maximum concentration (TSmax) in plasma is 1-2 hours. In women maximal concentration (CMax) of atorvastatin is 20% higher and area under curve “concentration-time” (AUC) is 10% lower than in men. The degree of absorption and plasma concentration increase in proportion to the dose.
The absolute bioavailability is about 14 % and systemic bioavailability of HMG-CoA reductase inhibitory activity is about 30 %. Low systemic bioavailability is due to presystemic metabolism in the mucosa of the gastrointestinal tract and/or during “primary passage” through the liver. Food intake reduces the rate and degree of drug absorption (by 25% and 9%, respectively), as evidenced by the results of Cmax and AUC determination, but decrease of LDL-C is similar to that of atorvastatin on an empty stomach. Despite the fact that after Atorvastatin administration in the evening its concentration in plasma is lower (Cmax and AUC, approximately by 30%) than after administration in the morning, decrease of LDL-C concentration does not depend on the time of day, when the drug is taken.
Distribution
The mean volume of distribution of atorvastatin is about 381 liters. The binding to plasma proteins is at least 98%. The ratio of content in erythrocytes/plasma is about 0.25, i.e. atorvastatin poorly penetrates into erythrocytes.
Metabolism
Atorvastatin is largely metabolized with the formation of ortho- and parahydroxylated derivatives and various β-oxidation products. In vivo ortho- and parahydroxylated metabolites have an inhibitory effect on HMG-CoA reductase comparable with that of atorvastatin. Approximately 70% of the decrease of HMG-CoA reductase activity is due to the action of active circulating metabolites. The results of in vitro studies suggest that hepatic CYPCA4 isoenzyme plays an important role in atorvastatin metabolism. This fact is supported by increased plasma concentrations of the drug with concomitant administration of erythromycin, which is an inhibitor of this isoenzyme. Studies have also shown that atorvastatin is a weak inhibitor of CYP3A4 isoenzyme. Atorvastatin has no clinically significant effect on plasma concentrations of terfenadine, which is metabolized primarily by CYPCA4 isoenzyme, therefore its significant effect on pharmacokinetics of other substrates of CYPCA4 isoenzyme is unlikely (see section “Interaction with other medicinal products”).
Atorvastatin and its metabolites are excreted mainly with bile after hepatic and/or extrahepatic metabolism (atorvastatin does not undergo marked hepatic recirculation). The half-life (T1/2) of atorvastatin is about 14 h, while its inhibitory effect against HMG-CoA reductase is about 70% determined by the activity of circulating metabolites and persists for about 20 – 30 hours due to their presence. After oral administration, less than 2% of the administered dose of the drug is detected in the urine.
Special groups of patients
Elderly patients
The plasma concentrations of atorvastatin in patients over 65 years old are higher (Cmax by about 40%, AUC by about 30%) than in adult patients of younger age. No differences in efficacy and safety of the drug, or achievement of the goals of hypolipidemic therapy in elderly patients compared to the general population have been found.
Children
There have been no studies of pharmacokinetics of the drug in children.
Inadequate renal function
Induced renal function has no effect on plasma concentrations of atorvastatin or its effect on lipid metabolism parameters; therefore, no dose change is required in patients with impaired renal function.
Atorvastatin is not excreted during hemodialysis due to intense binding to plasma proteins.
There have been no studies of atorvastatin use in patients with end-stage renal failure.
Liver function insufficiency
The drug concentration is significantly increased (Cmax approximately 16-fold, AUC approximately 11-fold) in patients with alcoholic cirrhosis (stage B on the Child-Pugh scale) (see section “Contraindications”).
Indications
– in combination with diet to decrease elevated levels of total chs, chs-LDL, apolipoprotein B and TG and increase HDL in patients with primary hypercholesterolemia, heterozygous familial and nonfamilial hypercholesterolemia and combined (mixed) hyperlipidemia (Fredrickson types IIa and IIb);
in combination with diet – in combination with diet for the treatment of patients with elevated serum TG levels (Fredrickson type IV) and patients with dysbetalipoproteinemia (Fredrickson type III) in whom diet therapy does not give an adequate effect;
To decrease total-Cs and LDL-C levels in patients with homozygous familial hypercholesterolemia when diet therapy and other non-pharmacological therapies are not effective enough.
Active ingredient
Composition
Polished film-coated tablets are pink, round, biconvex; on cross section the core of the tablet is white or almost white.
1 tablet atorvastatin (in the form of calcium salt)10 mg
Associated substances:
Lactose monohydrate (milk sugar) – 62 mg,
calcium carbonate – 33 mg,
povidone K30 (polyvinylpyrrolidone medium molecular) – 6 mg,
croscarmellose sodium (primellose) – 6.75 mg,
sodium stearyl fumarate – 1.5 mg,
colloidal silica (aerosil) – 0.75 mg,
microcrystalline cellulose – 30 mg.
Coating composition:
Opadray II (polyvinyl alcohol, partially hydrolyzed – 2.2 mg, macrogol (polyethylene glycol) 3350 – 0.6175 mg, talc – 1 mg, titanium dioxide (E171) – 0.9585 mg, soy lecithin (E322) – 0.175 mg, aluminum varnish based on indigo carmine dye – 0.003 mg, aluminum varnish based on azorubin dye – 0.0255 mg, aluminum varnish based on crimson dye [Ponzo 4R] – 0.0205 mg).
How to take, the dosage
Before Atorvastatin is prescribed, a standard hypolipidemic diet should be recommended for the patient, which should be followed for the duration of treatment.
The drug can be taken at any time of the day with food or regardless of the time of meals. The dose is selected taking into account the initial levels of LDL-C, the purpose of therapy and individual effect. At the beginning of treatment and/or during dose increase of Atorvastatin it is necessary to monitor plasma lipid levels every 2-4 weeks and adjust the dose accordingly.
The initial dose averages 10 mg once daily and thereafter varies from 10 mg to 80 mg once daily.
In concomitant use with cyclosporine the daily dose of Atorvastatin should not exceed 10 mg.
In primary hypercholesterolemia and mixed hyperlipidemia with elevated serum TG level (Fredrickson type IV) as well as in dysbetalipoproteinemia (Fredrickson type III) in most cases a daily dose of 10 mg once daily is sufficient. Significant therapeutic effect is usually observed after 2 weeks, the maximum therapeutic effect is usually observed after 4 weeks. With long-term treatment this effect is maintained.
In homozygous familial hypercholesterolemia the drug is indicated in a dose of 80 mg (4 tablets of 20 mg) once daily.
In patients with renal insufficiency and renal disease plasma concentrations of atorvastatin do not change, the degree of reduction of X-LDL is maintained, so no change in the drug dose is required.
In hepatic insufficiency the drug dose should be reduced.
There were no differences in safety, efficacy, or achievement of hypolipidemic therapy goals when using the drug in older patients compared to the general population.
Interaction
When concomitant use of atorvastatin with cyclosporine, HIV protease inhibitors (indinavir, ritonavir), antibiotics (erythromycin, clarithromycin, quinupristine/dalfopristine), antifungal drugs from azole group (fluconazole, Itraconazole, ketoconazole), nefazodone, fibric acid derivatives, nicotinic acid or diltiazem plasma concentration of atorvastatin increases, which increases the risk of myopathy with rhabdomyolysis and acute renal failure.
In concomitant administration of Atorvastatin and suspension containing magnesium hydroxide and aluminum hydroxide, plasma concentrations of Atorvastatin decreased by approximately 35%, but the degree of decrease in LDL-C levels did not change.
In concomitant use Atorvastatin does not affect pharmacokinetics of antipyrine (phenazone), therefore, interaction with other drugs metabolized by the same cytochrome P450 isoenzymes is not expected.
Concomitant use of colestipol decreases plasma concentration of atorvastatin by approximately 25%. However, hypolipidemic effect of combination of Atorvastatin and colestipol was superior to that of each drug separately.
The plasma Css of digoxin and Atorvastatin at a dose of 10 mg did not change when digoxin and Atorvastatin were repeatedly administered. However, when using digoxin in combination with Atorvastatin at a dose of 80 mg/day, digoxin concentration was increased by approximately 20%. The condition of patients should be monitored when using this combination.
In concomitant use of Atorvastatin and erythromycin (500 mg 4 times/day) or clarithromycin (500 mg 2 times/day), which inhibit CYP3A4 isoenzyme, increased plasma concentration of Atorvastatin was observed.
When concomitant administration of Atorvastatin (10 mg once daily) and azithromycin (500 mg once daily) the plasma concentration of Atorvastatin was not changed.
Atorvastatin had no clinically significant effect on plasma concentrations of terfenadine, which is metabolized primarily with participation of CYP3A4; in this regard, it seems unlikely that Atorvastatin can significantly affect pharmacokinetic parameters of other CYP3A4 isoenzyme substrates.
In concomitant use of Atorvastatin and oral contraceptives containing norethindrone and ethinylestradiol, a significant increase in AUC of norethindrone and ethinylestradiol by approximately 30% and 20% was observed, respectively. This effect should be considered when choosing an oral contraceptive for a woman receiving Atorvastatin.
Simultaneous use with drugs that reduce the concentration of endogenous steroid hormones (including cimetidine, ketoconazole, spironolactone) increases the risk of reduction of endogenous steroid hormones (caution is required with these combinations).
In studying the interaction of Atorvastatin with warfarin and cimetidine no signs of clinically significant interaction were found.
The pharmacokinetics of Atorvastatin at a dose of 80 mg and amlodipine at a dose of 10 mg did not change in equilibrium.
There have been no clinically significant adverse interactions of Atorvastatin and antihypertensive agents.
The concomitant use of Atorvastatin with protease inhibitors known as CYP3A4 inhibitors (grapefruit juice) was accompanied by an increase in plasma concentration of Atorvastatin, in this regard, consumption of this juice should be avoided.
Concomitant use of Atorvastatin with CYP3A4 isoenzyme inducers (efavirenz, rifampicin) leads to decreased plasma concentration of Atorvastatin.
Pharmaceutical incompatibility is not known.
Special Instructions
Before starting therapy with Atorvastatin, an attempt should be made to achieve control of hypercholesterolemia through adequate diet therapy, increasing physical activity, reducing body weight in obese patients and treating other conditions. A hypocholesterolemic diet must be followed by patients throughout the treatment period.
The use of HMG-CoA reductase inhibitors to decrease blood lipid levels may lead to changes in biochemical parameters reflecting liver function. Liver function should be monitored before the start of therapy, at 6 weeks, 12 weeks after the start of Atorvastatin and after each dose increase as well as periodically, e.g., every 6 months. Elevated serum hepatic enzyme activity may be observed during therapy with Atorvastatin. In such cases, patients should be monitored until normalization of liver enzymes activity. If ALT or ACT values are more than 3 times higher than GGN, it is recommended to reduce the dose of Atorvastatin or discontinue treatment. Active liver disease or persistent increase in aminotransferase activity of unclear genesis are contraindications to Atorvastatin administration.
Treatment with Atorvastatin may cause myopathy. In patients with widespread myalgia, muscle soreness or weakness and/or markedly increased CPK activity there is a possibility of myopathy (pain and weakness in muscles combined with increased CPK activity by more than 10 times compared to CHF). Atorvastatin therapy should be discontinued in case of marked increase of CPK activity or in the presence of confirmed or suspected myopathy.
The risk of myopathy during treatment with other drugs of this class was increased with concomitant use of cyclosporine, fibrates, erythromycin, nicotinic acid or azole antifungals. Many of these drugs inhibit CYP3A4 isoenzyme-mediated metabolism and/or drug transport. Atorvastatin is biotransformed by CYP3A4. Prescribing Atorvastatin in combination with fibrates, erythromycin, immunosuppressants, azole antifungal agents or nicotinic acid in hypolipidemic doses, the expected benefits and risks 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 doses of any drug. Periodic determination of CPK activity may be recommended in these situations, although such monitoring does not prevent the development of severe myopathy.
In Atorvastatin, as well as other drugs of this class, there have been cases of rhabdomyolysis with acute renal failure due to myoglobinuria. Atorvastatin therapy should be temporarily discontinued or completely discontinued in case of signs of possible myopathy or in presence of risk factor of renal failure development during rhabdomyolysis (for example, severe acute infection, arterial hypotension, serious operation, trauma, severe metabolic, endocrine and electrolyte disorders and uncontrolled convulsions).
Patients should be advised to seek immediate medical attention if they have unexplained muscle pain or weakness, particularly if there is malaise or fever.
Influence on driving and operating machinery
Patients should exercise caution when driving or operating machinery because there is a risk of dizziness when using Atorvastatin.
In patients with renal impairment
In patients with renal impairment and renal disease the plasma concentration of Atorvastatin does not change, the degree of LDL cholesterol reduction is maintained, so no change in the dose of the drug is required.
In case of liver function disorders
The drug is contraindicated in active liver disease; elevated liver enzymes activity of unclear genesis (more than 3 times as compared to CHF); in hepatic insufficiency (classes A and B according to Child-Pugh scale).
In case of hepatic insufficiency, the drug dose should be reduced.
Paediatric use
It is contraindicated in children under 18 years of age (efficacy and safety not established).
Contraindications
– active liver disease;
– increased liver enzyme activity of unclear genesis (more than 3 times compared to CHF);
– hepatic failure (grades A and B on the Child-Pugh scale);
– pregnancy;
– lactation period;
– age under 18 years (efficacy and safety not established);
– hypersensitivity to the components of the drug.
With cautiousness the drug should be used in patients with chronic alcoholism, history of liver disease, severe electrolyte balance disorders, endocrine and metabolic disorders, arterial hypotension, severe acute infections (sepsis), uncontrolled epilepsy, extensive surgical interventions, trauma, skeletal muscle diseases.
Side effects
Nervous system disorders: > 1% – insomnia, dizziness; < 1%- headache, asthenia, malaise, somnolence, nightmares, paresthesias, peripheral neuropathy, amnesia, emotional lability, ataxia, facial nerve palsy, hyperkinesias, migraine, depression, hypoesthesia, loss of consciousness.
Senses: < 1% – amblyopia, tinnitus, dry conjunctiva, accommodation disorder, retinal hemorrhage, deafness, glaucoma, parosmia, loss of taste sensation, perversion of taste.
Cardiovascular system side: > 1% – chest pain; < 1% – palpitations, vasodilation symptoms, orthostatic hypotension, increased BP, phlebitis, arrhythmia, angina pectoris.
With the hematopoietic system: < 1% – anemia, lymphoadenopathy, thrombocytopenia.
In the respiratory system: > 1% – bronchitis, rhinitis; < 1% – pneumonia, dyspnea, exacerbation of bronchial asthma, nasal bleeding.
Digestive system disorders: > 1% – nausea; < 1% – 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, liver dysfunction, rectal bleeding, melena, bleeding gums, tenesmus.
Musculoskeletal system side: > 1% – arthritis; < 1% – leg muscle cramps, bursitis, tenosynovitis, myositis, myopathy, arthralgia, myalgia, rhabdomyolysis, torticollis, muscle hypertonicity, joint contractures, joint swelling, tendopathy (in some cases with tendon rupture).
Urogenital system disorders: > 1% – urogenital infections, peripheral edema; < 1% – dysuria (incl. Pollakiuria, nycturia, urinary incontinence or urinary retention, imperative urge to urinate), leukocyturia, nephritis, hematuria, vaginal bleeding, nephrourolithiasis, metrorrhagia, epididymitis, decreased libido, impotence, ejaculation disorders.
Dermatological reactions: > 1% – alopecia, xeroderma, photosensitization, increased sweating, eczema, seborrhea, ecchymoses, petechiae.
From the endocrine system: < 1% – gynecomastia, mastodynia.
Metabolic side: < 1% – weight gain, aggravation of gout.
Allergic reactions: < 1% – skin itching, skin rash, contact dermatitis, rarely – urticaria, angioedema, facial edema, anaphylaxis, erythema multiforme exudative (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell syndrome).
Laboratory findings: < 1% – hyperglycemia, hypoglycemia, increased serum CPK, albuminuria.
Overdose
Treatment:There is no specific antidote, symptomatic therapy is carried out. Hemodialysis is ineffective.
Similarities
Weight | 0.030 kg |
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Manufacturer | North Star NAO, Russia |
Medication form | pills |
Brand | North Star NAO |
Other forms…
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