Lyprimar 20 mg tablets number 100

Author Ольга Кияница

2017-05-11

Amount in a package 100
Product form Pills
Manufacturer Pfizer Inc. (USA)
Registration certificate UA/2377/01/01
The main medicament Lymaris
morion code 199315

Lipparmar (Atorvastatin) Instructions for use

Composition

active ingredient : atorvastatin; 1 tablet contains calorie atorvastatin, equivalent to 10 mg or 20 mg, or 40 mg, or 80 mg of atorvastatin;
auxiliary substances: calcium carbonate; microcrystalline lactose monohydrate cellulose, croscarmellose sodium;polysorbate 80 hydroxypropyl cellulose; magnesium stearate film for film coating (hydroxypropylmethylcellulose, polyethylene glycol 8000, titanium dioxide (E 171), talc) simethicone emulsion (simethicone, emulsion-forming stearate, thickener, benzoic acid, sorbic acid).

Dosage form

Tablets coated with a film coat.

Basic physical and chemical properties:

White, round, coated film coated tablets with engraving "10", "20", "40" or "80" on one side and "ATV", "ATV", "ATV", "ATV" on the other, for tablets 10 mg, 20 mg, 40 mg and 80 mg, respectively.

Pharmacological group

Drugs that lower cholesterol and triglycerides in serum. HMG-CoA reductase inhibitors. Code ATX C10A A05.

Pharmacological properties

Pharmacodynamics.

Lyprimar is a synthetic hypolipidemic drug. Atorvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. This enzyme catalyzes the conversion of HMG-CoA into mevalonate, an early stage of cholesterol biosynthesis, which limits the rate of its formation.

Liprimar is a selective competitive inhibitor of HMG-CoA reductase, an enzyme, on which the rate of conversion of 3-hydroxy-3-methylglutaryl coenzyme A into mevalonate, a precursor substance of sterols, including cholesterol, depends.Cholesterol and triglycerides circulate in the bloodstream in a complex with lipoproteins. These complexes are separated by ultracentrifugation on HDL fractions (high density lipoproteins), LPPP (lipoproteins of intermediate density), LDL (low density lipoproteins) and LPONP (very low density lipoproteins). Triglycerides (TG) and cholesterol in the liver are included in the LPONP and released into the blood plasma for transportation to peripheral tissues. LDLs are formed by LPONP and catabolized by interaction with high affinity LDL receptors. Clinical and pathological anatomical studies show that elevated levels of total cholesterol (OX), LDL cholesterol (CHL-LDL) and apolipoprotein B (apo B) in blood plasma contribute to the development of atherosclerosis in humans and are risk factors for the development of cardiovascular disease, time as elevated levels of HDL cholesterol are associated with a reduced risk of cardiovascular disease.

In experimental models in animals, Lyprimar reduces the level of cholesterol and lipoproteins in the plasma by inhibition in the liver of HMG-CoA reductase and cholesterol synthesis and by increasing the amount of liver LDL receptors on the cell surface to enhance the absorption and catabolism of LDL; Liprimar also reduces the production of LDL and the amount of these particles. Liprimar reduces LDL cholesterol in some patients with homozygous familial hypercholesterolemia, that is, groups of people who rarely respond to treatment with other hypolipidemic drugs.

Numerous clinical studies have shown that elevated levels of total cholesterol, LDL cholesterol and apo B (membrane complex for LDL cholesterol) trigger the development of atherosclerosis. Similarly, levels of HDL cholesterol (and its transport complex - and on A) are associated with the development of atherosclerosis. Epidemiological studies have established that cardiovascular morbidity and mortality change in direct proportion to the level of total cholesterol and LDL cholesterol and inversely proportional to the level of HDL cholesterol.

Lyprimar reduces the level of total cholesterol, LDL cholesterol and apo B in patients with homozygous and heterozygous familial hypercholesterolemia, non-familial hypercholesterolemia and mixed dyslipidemia. Liprimar also reduces cholesterol levels of LPONP and TG, as well as leads to an unstable increase in HDL cholesterol and apolipoprotein A-1. Lyprimar reduces the level of total cholesterol, LDL cholesterol, cholesterol LPONP, apo B, triglycerides and cholesterol-free HDL cholesterol, and also increases HDL cholesterol levels in patients with isolated hypertriglyceridemia. Liprimar decreases cholesterol-blockage in patients with dysbetainipoproteinemia.

Like LDL, lipoproteins enriched in cholesterol and triglycerides, including LPONP, LPD and residues, can also contribute to the development of atherosclerosis. Elevated levels of triglycerides in blood plasma are often found in the triad with low levels of HDL cholesterol and small LDL fractions, as well as in combination with non-lipid metabolic risk factors for coronary heart disease. It has not been consistently shown that the overall level of triglycerides of the plasma alone is an independent risk factor for the development of coronary heart disease. Additionally, an independent effect of raising the level of HDL or reducing triglycerides was identified as a risk factor for coronary and cardiovascular morbidity and mortality.

Lyprimar, like some of its metabolites, is pharmacologically active in humans. The main place of action of atorvastatin is the liver, which plays a major role in the synthesis of cholesterol and clearance of LDL. The dose of the drug, in contrast to the systemic concentration of the drug, correlates better with the decrease in LDL cholesterol. Individual dose selection should be made depending on the therapeutic response (see Section "Method of administration and dose").

Pharmacokinetics.

Suction Liprimal is rapidly absorbed after oral administration and its maximum concentration in plasma is reached within 1-2 hours. The degree of absorption increases proportionally to the dose of the drug lyprimar. The bioavailability of atorvastatin (the starting product) is approximately 14%, and the systemic bioavailability of the inhibitory activity against HMG-CoA reductase is approximately 30%. The low systemic availability of the drug is associated with pre-system clearance in the mucous membrane of the gastrointestinal tract and / or pre-system biotransformation in the liver.Although food reduces the rate and extent of drug absorption by about 25% and 9% respectively, based on the C max and AUC values, LDL cholesterol lowering is similar whether or not lepimar is taken either with food or separately. When atorvastatin is administered in the evening, its plasma concentration is lower (approximately 30% for C max and AUC) than at morning reception. However, lowering LDL cholesterol levels is the same irrespective of the time of drug administration (see Section "Method of administration and dose").

Distribution. The average volume of distribution of the drug is about 381 liters. More than 98% of the drug is associated with plasma protein proteins. The concentration of blood / plasma is about 0.25, indicating a poor penetration of the drug into the erythrocytes. Based on observations from rats, it is believed that Lypymarum is able to penetrate breast milk (see sections "Contraindications", "Use during pregnancy or breastfeeding" and "Application features").

Metabolism. Lyprimar is extensively metabolized into ortho and parahydroxilated derivatives and various beta-oxidation products. In vitro studies of inhibition of HMG-CoA-reductase in ortho and parahydroxilated metabolites are equivalent to inhibiting Lypymar. Approximately 70% of the circulating inhibitory activity with respect to HMG-CoA reductase is associated with active metabolites. In vitro studies indicate the importance of the metabolism of the liprimar cytochrome P450 3A4 preparation, which is consistent with the elevated concentrations of the lypymar drug in human plasma after co-administration with erythromycin, a known inhibitor of this enzyme (see Section "Interaction with Other Drugs").

Excretion Liprimar and its metabolites are primarily derived from bile after hepatic and / or extrahepatic metabolism, but this drug obviously does not experience gastrointestinal recirculation. The half-life of leprimal from human plasma is approximately 14 hours, but the period of drinking decreases the inhibitory activity against HMG-CoA reductase from 20 to 30 hours due to the contribution of active metabolites. After taking the drug with urine, less than 2% of the dose is released.

Population of patients

Older patients. Plasma concentrations of Lyprimar are higher (approximately 40% for C max and 30% for AUC) in healthy elderly patients (over 65 years of age) than in younger adults. Clinical evidence suggests a greater reduction in LDL when any dose of the drug is used in elderly patients compared with younger people (see Section "Peculiarities of use").

Where are you. Pharmacokinetic data for a group of patients in childhood are absent.

Paul The concentration of Lyprimar in women's plasma is different from plasma concentrations (approximately 20% higher for C max and 10% lower for AUC). However, there is no clinically meaningful difference in the reduction of LDL cholesterol levels when using the Lypicram drug in men and women.

Abnormal kidney function. Kidney disease does not affect the concentration of liprimal in the blood plasma or the decrease in LDL cholesterol, and consequently, the dose adjustment of the drug for patients with impaired renal function is not required (see sections "Method of administration and dose", "application specifics").

Hemodialysis Despite the fact that patients with a terminal stage of kidney disease have not been investigated, it is considered that hemodialysis does not significantly increase the clearance of liprimar, since the drug is highly contagious with plasma protein proteins.

Hepatic failure. The concentration of Lyprimar in the blood plasma is markedly elevated in patients with chronic alcoholic liver disease. The values of C max and AUC are 4 times higher in patients with Class A liver disease on the Child-Pugh scale. In patients with Child-Pugh grade liver disease, the values of C max and AUC are increased approximately 16-fold and 11-fold respectively (see Section "Contraindications").

Table 1.

Effect of concurrently administered drugs on the pharmacokinetics of atorvastatin

Simultaneously used drugs and dosing regimen
Atorvastatin
Dose (mg)
Changing AUC &
Change C max &
# Ciclosporin 5.2 mg / kg / day, stable dose
10 mg once daily for 28 days
8.7 times
10.7 times
# Tipranavir 500 mg twice daily / ritonavir 200 mg twice daily, 7 days
10 mg of RD
9.4 times
8.6 times
# Telaprevir 750 mg every 8:00, 10 days
20 mg of RD
7,88 times
10.6 times
#, ‡ Saquinavir 400 mg twice daily / ritonavir 400 mg twice daily, 15 days
40 mg once daily for 4 days
3.9 times
4.3 times
# Clarithromycin 500 mg twice a day, 9 days
80 mg once daily for 8 days
4.4 times
5.4 times
# Darunavir 300 mg twice daily / ritonavir 100 mg twice a day, 9 days
10 mg once daily for 4 days
3.4 times
2.25 times
# Itraconazole 200 mg once daily, 4 days
40 mg of RD
3.3 times
20%
# Fosamprenavir 700 mg twice daily / ritonavir 100 mg twice daily, 14 days
10 mg once daily for 4 days
2.53 times
2.84 times
# Fosamprenavir 1400 mg 2 times a day, 14 days
10 mg once daily for 4 days
2.3 times
4,04 times
# Nelfinavir 1250 mg 2 times a day, 14 days
10 mg once daily for 28 days
74%
2.2 times
# Grapefruit juice, 240 ml once a day *
40 mg once daily
37%
16%
Diltiazem 240 mg once daily for 28 days
40 mg once daily
51%
without change
Erythromycin 500 mg 4 times a day, 7 days
10 mg once daily
33%
38%
Amlodipine 10 mg, single dose
80 mg once daily
15%
¯ 12%
Cimetidine 300 mg 4 times a day, 2 weeks
10 mg once daily for 2 weeks
¯ Less than 1%
¯ 11%
Koleslipol 10 mg 2 times a day, 28 weeks
40 mg once daily for 28 weeks
not defined
¯ 26% **
Maalox TC 30 ml once daily for 17 days
10 mg once daily for 15 days
¯ 33%
¯ 34%
Efavirenz 600 mg once daily for 14 days
10 mg for 3 days
¯ 41%
¯ 1%
# Rifampin 600 mg once daily, 7 days (with simultaneous administration) †
40 mg once daily
30%
2.7 times
# Rifampin 600 mg once daily, 5 days (in separate doses) †
40 mg once daily
¯ 80%
¯ 40%
# Gemfibrozil 600 mg twice daily for 7 days
40 mg once daily
35%
¯ Less than 1%
# Fenofibrate 160 mg once daily for 7 days
40 mg once daily
3%
2%
# Boecepvir 800 mg 3 times a day, 7 days
40 mg once daily
2.30 times
2.66 times

& Data indicated as a change in x times represent a simple relationship between the simultaneous use of drugs and the use of atorvastatin alone (i.e., 1-fold = unchanged). Data indicated in% change represent% difference in metrics when atorvastatin is administered separately (i.e., 0% = unchanged).

# For information on clinical significance, see the "Application Features" and "Interaction with Other Drugs and Other Interactions" sections.

* Significant increases in AUC (up to 2.5x) and / or C max (up to 71%) were reported with excessive consumption of grapefruit juice (750 ml - 1.2 liters per day or more).

** Single sample taken 8-16 hours after taking the drug.

† Due to the double-interaction mechanism of rifampin, the simultaneous use of atorvastatin with rifampin is recommended since it has been shown that delayed use of atorvastatin after rifampin is associated with a significant reduction in atorvastatin concentrations in plasma.

‡ The dose of the combination of saquinavir + ritonavir in this study is not a clinically applicable dose. Increased exposure to atorvastatin when used under clinical conditions is likely to be higher than that observed in this study.Therefore, it is advisable to use the drug with caution in the low required dose.

Table 2.

The effect of atorvastatin on the pharmacokinetics of concurrently used drugs

Atorvastatin
Simultaneously used drug and dosage regimen
Preparation / dose (mg)
Change in AUC
Change C max
80 mg once daily for 15 days
Antipyrin, 600 mg once
3%
↓ 11%
80 mg once daily for 14 days
Digoxin 0.25 mg once daily for 20 days
15%
20%
40 mg once daily for 22 days
Oral contraceptives 1 time per day, 2 months
    • norethisterone 1 mg
    • Ethinylestradiol 35 μg
28%
19%
23%
30%
10 mg once daily
Tipranavir 500 mg 2 times daily / ritonavir 200 mg 2 times a day, 7 days
without change
without change
10 mg once daily for 4 days
Fosamprenavir 1400 mg twice a day, 14 days
¯ 27%
¯ 18%
10 mg once daily for 4 days
Fosamprenavir 700 mg 2 times daily / ritonavir 100 mg 2 times daily, 14 days
without change
without change

# For information on clinical significance, see "Interacting with other drugs and other types of interactions."

Indications

Prevention of cardiovascular disease

For adult patients without clinically prominent coronary heart disease, but with several risk factors for coronary artery disease, such as age, smoking, arterial hypertension, low HDL or an early ischemic heart disease in a family history, librimar is indicated for:

  • reducing the risk of myocardial infarction
  • reducing the risk of stroke;
  • Reducing the risk of procedures for revascularization and angina pectoris.

For patients with type II diabetes and without clinically significant coronary heart disease, but with several risk factors for coronary heart disease, such as retinopathy, albuminuria, smoking, or arterial hypertension, the lipramar drug is indicated for:

  • reducing the risk of myocardial infarction
  • reducing the risk of stroke.

For patients with clinically pronounced coronary heart disease, librimar is indicated for:

  • reduction of the risk of non-lethal myocardial infarction
  • reduction of the risk of lethal and non-lethal stroke;
  • Reducing the risk of revascularization procedures;
  • reducing the risk of hospitalization due to congestive heart failure,
  • reducing the risk of angina pectoris.

Hyperlipidemia

In addition to the diet, to reduce elevated levels of total cholesterol, LDL cholesterol, apolipoprotein B and triglycerides, as well as to increase the level of HDL cholesterol in patients with primary hypercholesterolemia (heterozygous familial and non-familial) and mixed dyslipidemia (type IIa and IIb by Fredrickson classification) .
As an adjunct to a diet for the treatment of patients with elevated triglyceride levels in serum (type IV according to Fredrickson classification).
For the treatment of patients with primary dysbetainipoproteinemia (type III according to Fredrickson classification), in cases where diet compliance is not effective.
For Reduction of general cholesterol and LDL cholesterol in patsyentov homozyhotnoy semeynoy with hypercholesterolemia dopolnenye As for the second lipid-lowering methods of treatment (for example LDL apheresis) or methods of treatment If Such inaccessible.
As for diets for dopolnenye Noise level of general cholesterol, LDL cholesterol and apolipoprotein B in malchykov and devochek after beginning menstruation at age 10 to 17 years with hypercholesterolemia heterozyhotnoy semeynoy, after sootvetstvuyuschey If dyetoterapyy Results analyzov follows:

a) LDL cholesterol remains ³ 190 mg / dL or

b) LDL cholesterol ³ 160 mg / dL and:

As of family anamneze ymeyutsya Early cardio-vascular disease or two or more than others factors of risk of development of cardiovascular diseases in prysutstvuyut patsyenta childish age.

Contraindications

Disease Aktyvnoe liver, kotoroe include ustoychyvoe Can Increase transaminase activity pechenochnыh neyasnoy aetiology.
Hypersensitivity for anyone IZ components эtoho dasg funds.

Interaction with the second lekarstvennыmy funds and others types vzaymodeystvyy

Risk development myopathy IN TIME of treatment with statins povыshaetsya in sluchae simultaneously Application proyzvodnыh fybroevoy acid, lypydomodyfykatsyynyh doses of niacin, cyclosporin or moschnыh ynhybytorov CYP 3A4 (for example clarithromycin, ynhybytorov proteazy HIV and itraconazole) (cm. Sections "Features Application" and "Farmakolohycheskye properties") .

Moschnыe ynhybytorы CYP 3A4. Lyprymar metabolized by cytochrome P450 3A4. Application simultaneous preparation lyprymar with CYP 3A4 inhibitors moschnыmy Can Increase for lead concentrations of atorvastatin in plasma (see. Table 1 and podrobnuyu the info, pryvedennuyu below). Degree of interaction and action GAIN zavysyat such variability Impact on CYP 3A4. It should be on the Opportunity yzbehat simultaneously Application with moschnыmy inhibitor of CYP3A4 (for example, with cyclosporine, telytromytsynom, clarithromycin, delavyrdyn, styrypentolom, ketoconazole, voriconazole, itraconazole, Posakonazol and inhibitors protease HIV, the volume number rytonavyrom, lopynavyr, atazanavyrom, yndynavyrom, darunavyr). If impossible simultaneously avoided Application эtyh drugs with atorvastatinIt should rassmotret Application Ability less primary and maksymalnoy doses of atorvastatin. Also recommended conducting nadlezhaschyy Clinical MONITORING STATUS patsyenta (see. Table 1).

Umerennыe ynhybytorы CYP3A4 (for example erythromycin, diltiazem, verapamil and fluconazole) mogut povыshat concentrations of atorvastatin in plasma (see. Table 1). Application simultaneous erythromycin and statins accompanied Increase line development myopathy. Study drugs for interaction lekarstvennыh otsenki Effect of amiodarone or verapamil on atorvastatin have not been conducted. Known something amiodarone and verapamil podavlyayut activity of CYP3A4, and therefore, the simultaneous appointment эtyh drugs with atorvastatin resulted Can Increase Exposition for atorvastatin. Thus, while simultaneously Application atorvastatin and эtyh umerennыh ynhybytorov CYP3A4 sleduet rassmotret Ability purpose Less maksymalnыh doses of atorvastatin. Also recommended conducting Clinical MONITORING STATUS patsyenta.After the beginning of treatment or after correction inhibitor ego dozы recommended conducting Clinical MONITORING STATUS patsyenta.

Hreypfrutovыy juice. Containing more than one or components, kotoryya ynhybyruyut CYP 3A4 and mogut povыshat concentrations of atorvastatin in plasma, especially when yzbыtochnom consumption of grapefruit juice (more than 1.2 liter a day).

Clarithromycin. Value atorvastatin AUC Significantly povыshalos while simultaneously Application lyprymar a dose of 80 mg and clarithromycin (500 mg Double-in day) compared to primeneniem Only lyprymar drug (see. Section "Farmakolohycheskye properties"). Thus, patients, kotoryya prynymayut clarithromycin, sleduet with caution lyprymar Apply a dose of 20 mg (cm. Sections "Application Features " and "Method and Application dozы").

Kombynatsyya ynhybytorov proteases. Value atorvastatin AUC Significantly povыshalos while simultaneously lyprymar Application with Several kombynatsyyamy ynhybytorov proteazy HIV, as well as with an inhibitor of hepatitis C virus proteazy telaprevyr compared to primeneniem Only lyprymar drug (see. Section "Farmakolohycheskye properties"). Therefore for patsyentov, prynymayuschyh proteazy inhibitor of HIV + typranavyr rytonavyr inhibitor proteazy virus or hepatitis C telaprevyr, sleduet Application yzbehat simultaneously with drug lyprymar. It should be drug with caution assign patients, kotoryya prynymayut inhibitor proteazy lopynavyr HIV + and rytonavyr Apply Samoa neobhodymoy dose. For patsyentov, prynymayuschyh ynhybytorы proteazy sakvynavyr HIV + rytonavyr, darunavyr + rytonavyr, fosamprenavyr or fosamprenavyr + rytonavyr,lyprymar not dolzhna dose of 20 mg and prevыshat s Apply with caution (see. Sections "Application Features" and "Method and Application dozы"). When Application in patsyentov, prynymayuschyh proteazy inhibitor or HIV nelfynavyr proteazy inhibitor boceprevir hepatitis C virus dose lyprymar not dolzhna prevыshat 40 mg, and also recommended tschatelnoho Conducting Clinical Monitoring patients.

Itraconazole. Value atorvastatin AUC Significantly povыshalos while simultaneously Application lyprymar a dose of 40 mg and itraconazole 200 mg a dose (see. Section "Farmakolohycheskye properties"). Thus, patients, prynymayuschym itraconazole, sleduet bыt ostorozhnыmy, lyprymar prevыshaet If a dose of 20 mg (cm. Sections "Application Features" and "Method and Application dozы").

Cyclosporine. Atorvastatin and metabolites ego javljajutsja substrates transporter OATP1B1 . Ynhybytorы OATP1B1 (for example cyclosporine) mogut povыshat bioavailability of atorvastatin. Value atorvastatin AUC Significantly povыshalos while simultaneously Application lyprymar a dose of 10 mg and cyclosporine dose to 5.2 mg / kg / day compared to primeneniem Only lyprymar drug (see. Section "Farmakolohycheskye properties"). It should simultaneously yzbehat Application lyprymar and cyclosporine (see. Section "Features Application").

Medytsynskye Recommendations on Application lekarstvennыh drugs, vzaymodeystvuyuschyh podvedenы in Table 3 (see. Also divisions "Method and Application dozы", "Application Features", "Farmakolohycheskye properties").

Table 3.

Interaction lekarstvennыh assets related myopathy risk povыshennыm / rabdomyolyza

Preparations, vzaymodeystvuyut
Medytsynskye Recommendations on Application
Cyclosporine, ynhybytorы proteazy HIV (+ typranavyr rytonavyr) inhibitor of hepatitis C virus proteazy (telaprevyr)
Application of atorvastatin Yzbehat
Proteazy inhibitor of HIV (+ lopynavyr rytonavyr)
Apply with caution and a dose less neobhodymoy
Clarithromycin, itraconazole,
ynhybytorы proteazy HIV (sakvynavyr rytonavyr + * + darunavyr rytonavyr, fosamprenavyr, fosamprenavyr + rytonavyr)
Prevыshat dose of 20 mg of atorvastatin per night
Proteazy HIV inhibitor (nelfynavyr)
Inhibitors of hepatitis C virus proteazy (boceprevir)
Prevыshat dose of 40 mg of atorvastatin per night

* Apply with caution and a dose less neobhodymoy.

Hemfybrozyl. In connection with povыshennыm risk myopathy / rabdomyolyza while simultaneously ynhybytorov standard receiving HMG-CoA reductase s hemfybrozylom It should yzbehat sovmestnoho Application drug lyprymar with hemfybrozylom (see. Section "Features Application").

Other fibrates. Since known something myopathy risk of development of treatment TIME IN inhibitor of HMG-CoA reductase povыshaetsya simultaneously with standard receiving second fibratov, lyprymar sleduet Apply with caution when sovmestnom Using s second fybratamy (see. Section "Application Features).

Niacin. Risk occurrence pobochnыh phenomena co storony skeletnыh Can uvelychyvatsya muscles with use in kombynatsyy with niacin, and therefore, under such terms sleduet rassmotret Reduction Ability dozы drug lyprymar (see. Section "Features Application").

Rifampicin or others ynduktorы cytochrome P450 3A4. Application simultaneous preparation with inducers of cytochrome P450 3A4 ( эfavyrenz for example, rifampicin) may lead neustoychyvomu Reduction for concentrations of atorvastatin in plasma. Through the mechanism of interaction Dvoynykh ryfampyna recommended simultaneous Application lyprymar with ryfampynom, because the It would show something otsrochennoe Application of administering a drug after ryfampyna svjazano co znachytelnыm Reduction concentrations of atorvastatin in plasma.

diltiazema hydrochloride

Odnovremennыy pryem atorvastatin (40 mg) and diltiazema (240 mg) Increase accompanied concentrations of atorvastatin in plasma.

Cimetidine

As a result of research provedennыh pryznakov interaction cimetidine and atorvastatin have been detected.

antacids

Odnovremennыy pryem atorvastatin and oral suspensions antacids, soderzhascheho magnesium and aluminum hydroxide, accompanied Reduction concentrations of atorvastatin in plasma by 35%. With this action hypolypydemycheskoe atorvastatin unchanged.

colestipol

Concentration of atorvastatin plasma below (prymerno 25%) with simultaneous standard receiving atorvastatin and colestipol. With this action hypolypydemycheskoe kombynatsyy atorvastatin and colestipol prevыshala effect, kotoryya daet pryem kazhdogo IZ эtyh drugs separately.

Azithromycin

Simultaneous appointment of atorvastatin (10 mg 1 per day) and azithromycin (500 mg 1 per day) were soprovozhdalos Changes concentrations of atorvastatin in plasma.

Ynhybytorы transportnыh proteins

Ynhybytorы transportnыh proteins (for example cyclosporine) sposobnы povыshat Level systemnoy Exposition of atorvastatin (see. Table 1). Effect of suppression nakopytelnыh transportnыh proteins at concentrations of atorvastatin in liver cells of neyzvesten. If simultaneously avoided purpose эtyh impossible drugs, recommended dozы Reduction and Conducting Clinical Monitoring of the effectiveness of atorvastatin (see. Table 1).

Эzetymyb

Application эzetymyba in kachestve svyazыvayut monotherapy with development co phenomena storony mыshechnoy system, the volume number rabdomyolyza. Thus, while simultaneously эzetymyba Application development and atorvastatin risk эtyh phenomena increases. Recommended holds nadlezhaschyy Clinical MONITORING STATUS these patients.

Fusidic acid.

Study interaction atorvastatin and fuzydovoy acid is carried out. As sluchae and a second with a statin , the postmarketing period with simultaneous standard receiving atorvastatin and fuzydovoy acid nablyudalys phenomenon co storony mыshechnoy systems (including rabdomyolyz). Эtoho interaction mechanism remains neyzvestnыm. Patsyentы nuzhdayutsya in tschatelnom observation, can potrebovatsya Temporary pryostanovka of treatment with atorvastatin.

Digoxin.

When simultaneously Application mnohokratnыh doses of digoxin and lyprymar equilibrium concentrations of digoxin in the blood plasma povыshayutsya prymerno 20%. It should dolzhnыm image kontrolyrovat STATUS patsyentov, prynymayuschyh digoxin.

Oral contraceptives.

Application lyprymar simultaneous drug with contraceptive oralnыmy povыshalo importance AUC for norethisterone and ethinyl estradiol ( see. Section "Farmakolohycheskye properties"). These sleduet uchytыvat Increase in the election of oral contraceptives for Women, kotoraja prynymaet lyprymar.

Warfarin.

Clinical okazыval Lyprymar no significant action on prothrombin Application in Time at patsyentov, prohodyvshyh dlytelnoe Treatment with warfarin.

Colchicine.

With Application atorvastatin simultaneously with colchicine was reported cases of myopathy, including a volume rabdomyolyza, Therefore It should be with caution assign atorvastatin with colchicine.

Other Pharmaceuticals sredstva

Clinical research showed that simultaneous Application of atorvastatin and antihypertensive drugs and s Application in the course of estrogen-therapy zamestytelnoy not soprovozhdalos Clinical znachymыmy pobochnыmy effect. Studies interaction with the second drug is not carried out.

Application features

Skeletnыe muscle

Redkye messages acted on cases with acute renal rabdomyolyza insufficiency Due myoglobinuria with Application drug lyprymar and second lekarstvennыh drugs эtoho class. The presence in anamneze violations kidney function Can bыt factor of risk for development rabdomyolyza. Such patsyentы nuzhdayutsya in more than tschatelnom Monitoring to Identify violations co storony skeletnыh muscles.

Atorvastatin, How and others Preparations groups statins, myopathy vыzыvaet Sometimes, kotoraja How is determined to muscle pain or weakness in muscles The combination with indicators Increase CPK (CPK) something more than 10 times the upper boundaries Above rules. Simultaneous Application High-dose atorvastatin with opredelennыmy lekarstvennыmy drugs such cyclosporin As a moschnыe ynhybytorы CYP3A4 (for example clarithromycin, itraconazole and HIV protease ynhybytorы) povыshaet risk of myopathy / rabdomyolyza.

Redkye messages acted on cases immunological mediated necrotizing myopathy (YONM) - autoimmune myopathy, svyazannoy primeneniem with statins. YONM signs harakteryzuetsya follows: proximal muscle weakness and povыshennыy Level whey CPK in the blood kotoryya sohranyayutsya, Despite prekraschenye of treatment with statins; mыshechnaya biopsy vыyavlyaet nekrotyzyruyuschee Significantly myopathy without inflammation; Application with immunosuppressive funds polozhytelnaya observed dynamics.

Ability development myopathy sleduet rassmatryvat a dear patsyenta with diffuse myalgia, muscle slabostyu or boleznennostyu and / or znachytelnыm Increase CPK. It should Patsyentam porekomendovat nemedlenno Report cases of pain in the muscles, muscle weakness or boleznennosty neyzvestnoy aetiology, especially accompanied oschuschenyem If This nedomohanyya or Temperature Increase If signs or symptoms of the disease and muscle sohranyayutsya after prekraschenyya pryema drug lyprymar. Treatment sleduet prekratyt sluchae Increase in CPK urovnja, dyahnostyrovanyya or podozrenyya for myopathy.

Risk myopathy t Time of treatment drugs эtoho class povыshaetsya while simultaneously Application cyclosporine, proyzvodnыh fybroevoy acid, erythromycin, clarithromycin, inhibitors proteazy virus hepatitis C telaprevyr, kombynatsyy ynhybytorov proteazy HIV, the volume number sakvynavyr + rytonavyr, lopynavyr + rytonavyr, typranavyr + rytonavyr, darunavyr + rytonavyr, fosamprenavyr and fosamprenavyr + rytonavyr, as well as niacin group antimycotics or azoles. Doctors, kotoryya rassmatryvayut Ability kombynyrovannoy therapy drug lyprymar and proyzvodnыh fybroevoy acid, erythromycin, clarithromycin, kombynatsyy sakvynavyr + rytonavyr, lopynavyr + rytonavyr, darunavyr + rytonavyr, fosamprenavyru, fosamprenavyr + rytonavyr, antimycotics group azoles or lypydomodyfytsyruyuschey doses of niacin, dolzhnы tschatelno weigh Potential Benefits and risk,as well as tschatelno Monitor STATUS patsyentov on lyubыm pryznakov or symptomov pain, boleznennosty or weakness in muscles, especially in nachalnыh months of therapy and in techenye whatsoever IZ-Liboje periods tytrovanyya dozы Increase in the direction of any IZ drugs. It should rassmotret Application Ability nachalnыh and a number of doses of atorvastatin in podderzhyvayuschyh simultaneously with standard receiving vыsheukazannыmy lekarstvennыmy drugs (see. Section "Interaction with the second lekarstvennыmy funds and others types vzaymodeystvyy"). In such situations rassmatryvatsya Can definitions Ability Periodically CPK, but No Warranty, something such MONITORING pomozhet predotvratyt cases of severe myopathy.especially in nachalnыh months of therapy and in techenye whatsoever IZ-Liboje periods tytrovanyya dozы Increase in the direction of any IZ drugs. It should rassmotret Application Ability nachalnыh and a number of doses of atorvastatin in podderzhyvayuschyh simultaneously with standard receiving vыsheukazannыmy lekarstvennыmy drugs (see. Section "Interaction with the second lekarstvennыmy funds and others types vzaymodeystvyy"). In such situations rassmatryvatsya Can definitions Ability Periodically CPK, but No Warranty, something such MONITORING pomozhet predotvratyt cases of severe myopathy.especially in nachalnыh months of therapy and in techenye whatsoever IZ-Liboje periods tytrovanyya dozы Increase in the direction of any IZ drugs. It should rassmotret Application Ability nachalnыh and a number of doses of atorvastatin in podderzhyvayuschyh simultaneously with standard receiving vыsheukazannыmy lekarstvennыmy drugs (see. Section "Interaction with the second lekarstvennыmy funds and others types vzaymodeystvyy"). In such situations rassmatryvatsya Can definitions Ability Periodically CPK, but No Warranty, something such MONITORING pomozhet predotvratyt cases of severe myopathy.Section "Interaction with the second lekarstvennыmy funds and others types vzaymodeystvyy"). In such situations rassmatryvatsya Can definitions Ability Periodically CPK, but No Warranty, something such MONITORING pomozhet predotvratyt cases of severe myopathy.Section "Interaction with the second lekarstvennыmy funds and others types vzaymodeystvyy"). In such situations rassmatryvatsya Can definitions Ability Periodically CPK, but No Warranty, something such MONITORING pomozhet predotvratyt cases of severe myopathy.

It was reported cases of myopathy in volume while simultaneously including rabdomyolyza Application atorvastatin with colchicine, colchicine Therefore with atorvastatin It should assign patsyentam with caution (see. Section "Interaction with the second lekarstvennыmy funds and others types vzaymodeystvyy").

Therapy lyprymar It should be temporarily or completely prekratyt a dear patsyenta with ostrыm, sereznыm STATUS, ukazыvaet on Development myopathy, or in the availability factor of risk of development renal insufficiency Due rabdomyolyza (for example tyazhelaya Acute infection, hypotension, Surgical operations, trauma, Heavy metabolic, эndokrynnыe and эlektrolytycheskye disorders, as well as nekontrolyruemыe spasms).

Violation liver function

It has been shown that statins, as well as some other hypolipidemic therapeutic agents, are associated with a deviation from the norm of biochemical parameters of liver function. A steady increase (more than 3 times the upper limit of the normal range, which occurred 2 times or more) of serum transaminases was observed in 0.7% of patients who received liprimar in clinical trials. The incidence of these abnormalities was 0.2%, 0.2%, 0.6% and 2.3% for doses of 10, 20, 40 and 80 mg, respectively.

During the clinical studies of the drug, one patient developed jaundice. The increase in liver function tests (FPP) in other patients was not associated with jaundice or other clinical signs and symptoms. After reducing the dose in the administration or discontinuation of the drug, levels of transaminases returned to levels prior to treatment or approximately these levels without residual effects. 18 out of 30 patients with a steady increase in liver function tests continued to treat liprimar at lower doses.

Before starting treatment with Lypymar, it is advisable to obtain the results of liver enzyme tests and reassess analyzes in case of clinical need. There were rare post-traumatic reports of cases of lethal and non-lethal hepatic insufficiency in patients taking statin group drugs, including atorvastatin. In the case of severe liver damage with clinical symptoms and / or hyperbilirubinemia or jaundice, when using the drug, liprimar should be stopped immediately. If alternative etiology is not defined, treatment should not be re-started.

Liprimar should be administered with caution to patients taking significant amounts of alcohol and / or with a history of liver disease. Liprimar is contraindicated in patients with active liver disease or persistent elevation in the activity of hepatic transaminases of unknown etiology (see Section "Contraindications").

Endocrine function

It was reported that an increase in HbA1c and glucose concentration in fasting blood serum was reported with the use of HMG-CoA reductase inhibitors, including the liprimal drug.

Statins inhibit cholesterol synthesis and theoretically may weaken the secretion of adrenal and / or gonadal steroids.Clinical studies have shown that Lyprimar does not reduce the basal concentration of cortisol in the plasma and does not damage the reserve of the adrenal glands. The effect of statins on the fertility of sperm has not been studied in sufficient numbers of patients. It is not known how the drug affects, and in general, affects the system of "gonads-hypophysis-hypothalamus" in women in the premenopausal period. Care should be taken when co-administering a statin group with drugs that can lower the levels or activity of endogenous steroid hormones, such as ketoconazole, spironolactone and cimetidine.

Application to patients with recent cases of stroke or transient ischemic attack

In post-hoc analysis of the SPARCL study (Stroke Prevention by Aggressive Reduction in Cholesterol Levels), during which 80 mg lepimarum versus placebo was administered to 4,731 patients without coronary heart disease who had a history of stroke or transient ischemic attack during the previous 6 months, a high incidence of hemorrhagic stroke was observed in the group of patients receiving 80 mg lepimarom in comparison with the placebo group (55 cases, 2.3% in the atorvastatin group n compared with 33 cases, 1.4% in the placebo group; avg: 1.68, 95% DI: 1,09, 2,59; p = 0,0168).The incidence of lethal hemorrhagic stroke was similar in all treatment groups (17 and 18 for atorvastatin and placebo groups, respectively). The incidence of non-lethal hemorrhagic stroke was significantly higher in the group of patients receiving atorvastatin (38, 1.6%) compared with placebo (16, 0.7%). Some initial characteristics, including the presence of cases of hemorrhagic and lacunar stroke during the inclusion in the study, were associated with a higher incidence of hemorrhagic stroke in the group of patients receiving atorvastatin (see Section "Adverse Reactions").

Of the 39,828 patients who received lepimar in clinical trials, 15,813 (40%) of patients were 65 years of age and 2800 (7%) of patients were 75 years of age. There was no overall difference in the safety and efficacy of the drug between these patients and young patients, nor did any difference in response to treatment in elderly patients and young patients in other clinical experience have been reported, however, it can not be excluded that some older patients may be more sensitive . Since the elderly (65 years) is a factor in myopathy predisposition, caution should be exercised in prescribing Lyprimar to elderly people.

Hepatic failure

Liprimar is contraindicated in patients with active liver disease, including a persistent increase in the activity of hepatic transaminases of unclear etiology (see sections "Contraindications" and "Pharmacological properties").

Before treatment

Atorvastatin should be administered with caution to patients with a tendency to develop rhabdomyolysis. Before initiating treatment with statins in patients prone to developing rhabdomyolysis, the level of CK should be determined when:

  • impaired kidney function
  • hypothyroidism of the thyroid gland;
  • hereditary disorders of the muscular system in a family or personal history
  • cases of toxic effects of statins or fibrates on muscles transmitted in the past;
  • past diseases of the liver and / or consuming large amounts of alcohol.

For elderly patients (over 70 years of age), the need for these activities should be evaluated taking into account the presence of other factors predisposed to the development of rhabdomyolysis.

An increase in the level of the drug in plasma, possibly in particular, in the case of interaction and application of special populations of patients, including patients with hereditary diseases.

In such cases, it is recommended to assess the relationship between risks and the possible benefits of treatment and to conduct clinical monitoring of patients' condition. If prior to treatment, the level of CK is significantly elevated (more than 5 times the GVM), treatment should not be started.

Measurement of the level of KFK

The level of CPK should not be determined after intense physical activity, or if there are any possible alternative causes for increasing the MC level, as this may complicate the decryption of the results. If at the initial level there is a significant increase in the CK (exceeding the upper limit of the norm more than 5 times), then in 5-7 days it is necessary to re-determine to confirm the result.

During the treatment

Patients should be aware of the need to immediately report the development of muscle pain, libido, or weakness, especially if they are accompanied by anemia or fever.

If these symptoms occur during treatment with atorvastatin, it is necessary to determine the level of QC in this patient. If the level of CK is significantly elevated (exceeding 5 times the BMD), treatment should be discontinued.

The expediency of discontinuation of treatment should also be considered if the increase in the level of CK does not reach a five-fold increase in BMI, but the muscle symptoms are severe and cause daily unpleasant sensations.

After the disappearance of symptoms and the normalization of the level of CK, one can consider the possibility of renewal of atorvastatin treatment or the initiation of treatment with alternative statins, provided that the minimum possible dose is applied and careful monitoring of the patient's condition.

Treatment with atorvastatin should be discontinued if there is a clinically significant increase in CK level (exceeding the upper limit of the norm by more than 10 times) or in the case of a diagnosis of rhabdomyolysis (or suspected rhabdomyolysis).

Simultaneous use with other medications

The risk of developing rhabdomyolysis is increased when atorvastatin is co-administered with some drugs that can increase the concentration of atorvastatin in the blood plasma. Examples of such drugs include potent CYP3A4 inhibitors or transport proteins, cyclosporin, telithromycin, clarithromycin, delivirin, stiripentol, ketoconazole, voriconazole, itraconazole, posaconazole, and HIV protease inhibitors, including ritonavir, lopinavir, atazanavir, indinavir, daranavir. At simultaneous application with gemfibrozil and other derivatives of fibrous acid, erythromycin, niacin and ezetimiba, there is also a risk of myopathy. If possible, other medications (not interacting with atorvastatin) should be used instead of the above.

If atorvastatin and these drugs are to be treated concurrently, the benefits and risks of simultaneous treatment should be weighed carefully. If patients take medications that increase the concentration of atorvastatin in plasma, it is recommended that the dose of atorvastatin be reduced to a minimum. In addition, if a potent CYP3A4 inhibitor is to be used, consideration should be given to the use of a lower initial dose of atorvastatin. It is also recommended to conduct proper clinical monitoring of these patients.

It is not recommended to simultaneously appoint atorvastatin and fusidic acid, so it is worth considering the possibility of temporarily withdrawing atorvastatin during the treatment with fusidic acid.

Interstitial lung disease

During treatment, certain cases of development of interstitial lung disease were described by certain statins (especially during long-term treatment). The symptoms of this disease include shortness of breath, unproductive cough and general deterioration of well-being (fatigability, weight loss and fever). In case of suspicion of interstitial lung disease, statins should be discontinued.

Fillers

The composition of the drug is lycophora. This drug should not be taken in patients with rare hereditary diseases associated with galactose intolerance, lupus lactase deficiency, or malabsorption of glucose-galactose. The therapy of lipid modifying drugs should be one of the components of complex therapy for patients with a significantly increased risk of developing atherosclerotic vascular disease through hypercholesterolemia. Drug therapy is recommended as a supplement to the diet, when the result of observing a diet restricting the consumption of saturated fats and cholesterol, as well as the use of other non-pharmacological measures was not enough. Patients with ischemic heart disease or several risk factors for developing coronary heart disease may start taking liprimal at the same time as observing the diet.

Application limitation

Liprimar has not been studied in conditions where the main deviation from the norm from the side of the lipoproteins is an increase in the level of chylomicrons (types I and V according to the Fredrickson classification).

Use during pregnancy or breastfeeding

Pregnancy

Liprimar is contraindicated in pregnant women and women who can become pregnant. Statins can cause fetal harm when applied to pregnant women. Liprimar can be used in women of reproductive age only if it is very unlikely that such patients become pregnant and they are informed about potential risk factors. If a woman has become pregnant during the treatment of Lypicrim, an immediate withdrawal of the drug and re-consultation of the patient with potential risk factors for the fetus should be discontinued and there is no known clinical benefit from continued use of the drug during pregnancy.

With normal pregnancy, levels of serum cholesterol and triglycerides increase. Admission of hypolipidemic drugs during pregnancy will not have a beneficial effect, since cholesterol and its derivatives are essential for the normal development of the fetus. Atherosclerosis is a chronic process, and, consequently, a break in taking hypolipidemic drugs during pregnancy should not have a significant effect on the results of long-term treatment of primary hypercholesterolemia.

Adequate and well-controlled studies of atorvastatin use during pregnancy have not been conducted. There were rare reports of congenital anomalies after the fetal exposure to statins. In a prospective observation, approximately 100 cases of pregnancy in women treated with other statin group drugs, the incidence of congenital fetal abnormalities, abortions and intrauterine deaths / stillbirths did not exceed the frequency expected for the general population. However, this study could only exclude a 3-4-fold increase in the risk of congenital anomalies of fetal development compared with background frequency. In 89% of these cases, treatment began before pregnancy and stopped at the first trimester after the discovery of pregnancy.

Breast feeding period

It is not known that atorvastatin penetrates breast milk, but it is known that a small amount of another drug of this class penetrates breast milk. Since statins are potentially capable of causing serious adverse reactions in breastfed infants, women who require liprimal treatment should not breast-feed their infants (see Section "Contraindications").

Ability to influence the speed of reaction when driving motor vehicles or other mechanisms

It has a very small effect on the reaction speed when driving motor vehicles or other mechanisms.

Method of administration and dose

Hyperlipidemia (heterozygous familial and non-familial) and mixed dyslipidemia (Type IIa and IIb by Fredrickson classification)

The recommended initial dose of Lyprimar is 10 or 20 mg once daily. For patients who require a significant reduction in LDL cholesterol (more than 45%), therapy can be started with a dose of 40 mg once a day. The dosage range of the drug is between 10 and 80 mg of lyprimar once a day. The drug can be taken at a single dose at any time and regardless of food intake. Initial and supportive doses of lypymar should be selected individually, depending on the purpose of the treatment and the response. After initiation of treatment and / or after titration of the dose of Lyprimar, lipid levels should be analyzed over a period of 2 to 4 weeks and appropriate dose correction.

Heterozygotic familial hypercholesterolemia in children of childhood (aged 10-17 years)

The recommended initial dose of Lyprimar is 10 mg / day, the maximum recommended dose is 20 mg / day (doses greater than 20 mg in this group of patients have not been studied). Doses of the drug should be selected individually in accordance with the recommended purpose of treatment. The dose adjustment should be done at intervals of 4 weeks or more.

Homozygous familial hypercholesterolemia

The dose of lypymar in patients with homozygous familial hypercholesterolemia is 10 to 80 mg per day. Liprimar should be used as an add-on to other hypolipidemic treatments (eg, apheresis LDL), or if hypolipidemic treatments are unavailable.

Simultaneous hypolipidemic therapy

Liprimar can be used with sequestrants of bile acids. The combination of HMG-CoA reductase inhibitors (statins) and fibrates should be used with caution in general (see sections "Peculiarities of use", "Interaction with other drugs and other types of interactions").

Dosage for patients with impaired kidney function

Kidney infections do not affect either plasma concentrations or LDL cholesterol levels when using the lipprimal drug;consequently, dose adjustment of the drug for patients with impaired renal function is unnecessary (see sections "Peculiarities of use", "Pharmacokinetics").

Dosage for patients taking cyclosporine, clarithromycin, itraconazole or certain protease inhibitors

Lypymar treatment should be avoided in patients taking cyclosporine or HIV protease inhibitors (tyranenavir + ritonavir), or a hepatitis C virus protease inhibitor (telaprevir). Liprimar should be prescribed with caution to HIV patients who take lopinavir + ritonavir and use it at the most appropriate dose.In patsyentov, prynymayuschyh clarithromycin, itraconazole or in patsyentov with HIV, kotoryya prynymayut in kombynatsyy sakvynavyr + rytonavyr, darunavyr + rytonavyr, fosamprenavyr or fosamprenavyr + rytonavyr, terapevtycheskuyu dose lyprymar sleduet Limit dose of 20 mg, and also recommended conducting neobhodymыe Clinical Survey for Provision Application maleyshey neobhodymoy dozы lyprymar. In patsyentov, prynymayuschyh inhibitor proteazy HIV nelfynavyr or inhibitor proteazy virus hepatitis C boceprevir, of treatment lyprymar sleduet Limit the dose to 40 mg, and also recommended Conducting sootvetstvuyuschyh Clinical obsledovanyy to implement the Application maleyshey neobhodymoy dozы lyprymar (see. Section "Features Application " and "Interaction s second lekarstvennыmy funds and others types vzaymodeystvyy").

Where are you

Safety and Efficiency in the preparation of patsyentov aged 10-17 years with hypercholesterolemia heterozyhotnoy semeynoy bыla of research in Clinical Research kontrolyruemom prodolzhytelnostyu malchykov in 6 months, adolescents and devushek after the beginning of menstruation. Patsyentы, kotoryya poluchaly Treatment lyprymar drug, in general ymely shaped Profil nezhelatelnыh reactions patsyentov, poluchavshyh placebo. Infectious disease bыly theme nezhelatelnыmy phenomenon, kotoryya chashche Total nablyudalys in obeyh group nezavysymo from otsenki cause and sledstvennoy connection. The group within this patsyentov yssledovalys dozы not more than 20 mg of the drug.In this research uzkom kontrolyruemom It would not been detected significant drug Effect on growth or Sexual sozrevanye malchykov or on the Duration of the menstrual cycle in devushek (cm. Sections "Side reactions" "Method and Application dozы"). It should Devochek-adolescent prokonsultyrovat on pryemlemыh methods kontratseptsyy in techenye lyprymar period of treatment (see. Section "Application in the period of pregnancy or feeding grudju" and "Application Groups in otdelnыh patsyentov").Application Groups in otdelnыh patsyentov ").Application Groups in otdelnыh patsyentov ").

Lyprymar yssledovalas not controlled in Clinical Research, kotoryya included patsyentov adolescents age or patsyentov at age 10 years.

Clinical Efficiency drug in doses up to 80 mg / day in the Year 1 techenye bыla otsenena in nekontrolyruemom research in patsyentov with homozyhotnoy semeynoy hypercholesterolemia in kotoryya bыly vklyuchenы 8 patsyentov childish age (see. Section "Homozyhotnaya semeynaya giperholesterinemija").

Overdose

Spetsyfycheskoho of treatment peredozyrovky drug lyprymar not. In cases peredozyrovky patsyenta It should be symptomatic and at lechyt Need Apply podderzhyvayuschye measures. By degrees svyazыvanyya Peak drug plasma proteins with Ozhydiv It should not ride height Significantly GAIN drug lyprymar pomoshchju with hemodialysis.

Side reactions

In connection with the topic, something Clinical research provodyatsya in terms, kotoryya koleblyutsya widely Limit, the frequency of occurrence nezhelatelnыh reactions nablyudaemыh IN TIME Clinical of research dasg drugs, impossible napryamuyu sravnyvat with indicators, poluchennыmy in the course of Clinical of research of the second drug, and îíè mogut not otrazhat Indicator klynycheskoy frequency observed in practice.

Bazeilles data in placebo-controlled Clinical drug research lyprymar Among 16,066 patsyentov (8755 and 7311 poluchaly lyprymar poluchaly placebo vozrastnoy The range 10-93 years, 39% women, 91% evropeoydnoy rasы 3% nehroydnoy rasы 2% azyatskoy rasы 4% others) with medyanoy of treatment, amounted to 53 weeks, 9.7% patsyentov, poluchavshyh lyprymar, 5% and 9 patsyentov, poluchavshyh placebo drug because prekratyly Application nezhelatelnыe reactions, such nezavysymo prychynnoy connection with the drug. Five most rasprostranennыh pobochnыh эffektov in patsyentov, poluchavshyh Treatment drug lyprymar, kotoryya led prekraschenyyu Application for drug and sluchalys with chastotoj Above, than in the placebo group, bыly, myalgia (0.7%), diarrhea (0.5%), nausea (0.4%) Increase urovnja alanynamynotransferazы (ALT) (0.4%) and pechenochnыh enzymes (0.4%).

In patsyentov, poluchavshyh Treatment drug lyprymar in placebo-controlled research (n = 8755), chashche Total nablyudalys Such Side reactions (incidence cases of 2% or more than a Above, than placebo) nezavysymo from prychynnoy communication: nasopharyngitis (8, 3% ), arthralgia (6.9%), diarrhea (6.8%), pain in the extremities (6.0%) and infection mochevыvodyaschyh tract (5.7%).

Table 4 summyruetsya frequency Clinical nezhelatelnыh reactions nezavysymo from prychynnoy communication, REGISTERED 2% patsyentov or bolshe and from chastotoj, Above, than in the placebo group in patsyentov, poluchavshyh Treatment drug lyprymar (n = 8755), the dannыm 17 placebo-controlled research.

Table 4.

Clinical nezhelatelnыe reaction, voznykavshye 2% and more than patsyentov, poluchavshyh Treatment lyprymar any dose of the drug, and from chastotoj, Above, than placebo from nezavysymo prychynnoy communication (patsyentov%).

Nezhelatelnaya reaction *
Luba dose N = 8755
10 mg N = 3908
20 mg N = 188
40 mg N = 604
80 mg N = 4055
Placebo N = 7311
nasopharyngitis
8.3
12.9
5.3
7
4.2
8.2
arthralgia
6.9
8.9
11.7
10.6
4.3
6.5
diarrhea
6.8
7.3
6.4
14.1
5.2
6.3
Pain in the extremities
6
8.5
3.7
9.3
3.1
5.9
Mochevыvodyaschyh tract infection
5.7
6.9
6.4
8
4.1
5.6
indigestion
4.7
5.9
3.2
6
3.3
4.3
nausea
4
3.7
3.7
7.1
3.8
3.5
Muscle-pain skeletnыe
3.8
5.2
3.2
5.1
2.3
3.6
mыshechnыe spazmы
3.6
4.6
4.8
5.1
2.4
3
myalgia
3.5
3.6
5.9
8.4
2.7
3.1
bessonnytsa
3
2.8
1.1
5.3
2.8
2.9
farynholarynhealnaya pain
2.3
3.9
1.6
2.8
0.7
2.1
* Nezhelatelnaya reaction> 2% more than at any dose, placebo something

K nezhelatelnыh second reactions was reported at kotorыh IN TIME placebo-controlled of research, include:

Sharing violations: nedomohanye, pyreksyya;

co storony pyschevarytelnoy system: kyshechnыy gastrointestinal discomfort, belch, flatulence, hepatitis, cholestasis,

Co storony osteo-mыshechnoy system: muscle-skeletnыe pain, muscle peak times Fatigue, pain in shee, opuhanye joints, tendynopatyya (Sometimes zatrudnena gap suhozhylyya)

storony metabolism and co POWER: Increase transaminases, Deviations from norms funktsyonalnыh liver tests, alkaline phosphatase urovnja Increase in blood Increase of CPK activity, hyperglycemia;

co storony nervous system: koshmarnыe snovydenyya;

co storony dыhatelnoy systems: Bow bleeding;

storony kozhy co ee and paranasal: krapyvnytsa

co storony bodies of view: nechetkost of view, breach of view;

co storony organs of hearing and equilibrium: the noise in the ears

co storony mochepolovoy system: leykotsytouryya;

Co storony Reproductive system and of milk glands, gynecomastia.

The frequency of occurrence pobochnыh reactions opredelyaly follows way: often (> 1/100, <1/10); not often

(> 1/1000, <1/100); redkye (> 1/10000, <1/1000) ; Very redkye (<1/10000).

Violation functions nervous system: Headache pain is often rare: dizziness, paresthesia, hypestezyya, dyshevzyya, amnesia, rarely, peryferycheskye neuropathy.

Violation function of the gastrointestinal tract, constipation often infrequent pancreatitis, vomiting.

Violation functions supporting-dvyhatelnoho apparatus and soedynytelnoy tissue, often pain in the joints, pain in the back rarely, myopathy, myositis, rabdomyolyz.

Sharing violations, often weakness, pain in the chest, peryferycheskye edema, Fatigue.

Violation metabolism and POWER: hypoglycemia often, Increase Fire-proof compounds PE anorexia.

Violation liver function and bile bubbles: Extraordinary rarely: pechenochnaya failure.

Co storony kozhy and soedynytelnoy tissue, often kozhnыe vыsыpanyya, itching, edema alopetsyya redkye anhyonevrotycheskyy, bulleznыy dermatitis (including multyformnaya эrytema), Stevens-Johnson syndrome and toxic epidermal nekrolyz.

Dыhatelnoy system disorders, thoracic organs and cells mediastinum, often, pain in the throat and larynx.

Disorders of the blood system and lymfatycheskoy system: redkye: thrombocytopenia.

Ymmunnoy system disorders: often allerhycheskye reaction; Extraordinary rarely, anaphylaxis.

Disorders bodies of view, often zatumanyvanye view.

Changes laboratornыh analyzov results: Uncommon: Deviations results funktsyonalnыh liver tests, blood CPK activity Increase polozhytelnыy often the result of analysis on the Content leykotsytov in urine.

As and when the second ynhybytorov Application of HMG-CoA reductase in patsyentov, prynymavshyh atorvastatin was observed activity of transaminases Increase blood sera. These Changed Usually bыly vыrazhennыmy weak, and not vremennыmy nuzhdalys intervention or treatment. Clinical activity znachymoe Increase transaminases blood sera (prevыshenye upper boundaries norms something more than 3 times) nablyudaly 0.8% patsyentov, prynymavshyh atorvastatin. This dose-dependent Increase dolzhna nature and in obratymыm It would vseh patients.

2.5% patsyentov, prynymavshyh atorvastatin, CPK activity nablyudaly Increase blood sera, something more than something 3 times prevыshala verhnyuyu border rules. This observation sovpadaet s Application in the second ynhybytorov HMG-CoA reductase in the course Clinical research. At 0.4% patsyentov, poluchavshyh atorvastatin nablyudalys level, prevыshayuschyh verhnyuyu border norms something more than 10 times.

Side reactions, kotoryya IN TIME Clinical voznykly of research: mochevыh tract infection, saharnыy diabetes, stroke.

In research ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial), kotoroe included 10,305 participants (vozrastnoy The range 40-80 years, 19% women, 94.6% evropeoydnoy rasы representatives, representatives nehroydnoy 2.6% rasы 1.5% southwest azyatskoho origin and 1.3% smeshannoho origin / second) kotoryya poluchaly Treatment lyprymar in ezhednevno dose of 10 mg (n = 5168) or placebo (n = 5137), Profil safety and tolerability patsyentov group, kotoryya poluchaly lyprymar bыl Compare with takovыm in in the placebo group techenye posleduyuscheho observation period with medyanoy Duration 3.3 year.

In research CARDS (Collaborative Atorvastatin Diabetes Study), 2838 patsyentov kotoroe included (in vozrastnom bands 39-77 years, 32% women, 94.3% evropeoydnoy representatives rasы 2.4% South azyatskoho origin, 2.3% African karybskoho origin and 1% others) with saharnыm diabetes II type, poluchavshyh Treatment drug lyprymar a dose of 10 mg per day (n = 1428) or placebo (n = 1410), not was observed nykakoy raznytsы a total often is nezhelatelnыh reactions or sereznыh nezhelatelnыh reactions Between Groups techenye period of treatment in posleduyuscheho observation with medyanoy Duration and 3.9 year. None of kakyh not rabdomyolyza cases was reported.

Studies in TNT (Treating to New Targets Study / Research) kotoroe included 10001 patsyenta (vozrastnoy The range 29-78 years, 19% women, 94.1% evropeoydnoy representatives rasы, 2.9% nehroydnoy rasы representatives, representatives 1.0% monholoydnoy rasы and 2.0% others) with Clinical vыrazhennoy yshemycheskoy heart illness, poluchavshyh lyprymar a dose of 10 mg per day (n = 5006) or lyprymar a dose of 80 mg per day (n = 4995), more than nablyudalys sereznыe nezhelatelnыe reactions and cases otmenы drug because of the reactions in the group pobochnыh patsyentov, poluchavshyh High dozы atorvastatin (92, 1.8%; 4 97, 9.9% respectively) compared to hruppoy patsyentov, poluchavshyh Low dozы drugs (69 1.4% 404 8.1% respectively) in techenye posleduyuscheho observation period with medyanoy Duration 4.9 year.Ustoychyvыe urovnja Increase transaminases (3 times or more than Above upper boundaries norm range, Double-techenye in 4-10 days) nablyudalys in 62 (1.3%) man, kotoryya poluchaly dose of atorvastatin 80 mg and in 9 (0.2% ) persons, poluchavshyh atorvastatin dose of 10 mg. Increase CK (or 10 times more than the normal boundaries Above upper bands) bыly a whole series, but in the group bыly Above patsyentov, poluchavshyh High dozы atorvastatin (13, 0.3%) compared to hruppoy patsyentov, poluchavshyh Low dozы atorvastatin (6 , 0.1%).poluchavshyh High dozы atorvastatin (13, 0.3%) compared to hruppoy patsyentov, poluchavshyh Low dozы atorvastatin (6, 0.1%).poluchavshyh High dozы atorvastatin (13, 0.3%) compared to hruppoy patsyentov, poluchavshyh Low dozы atorvastatin (6, 0.1%).

In research IDEAL (Incremental Decrease in Endpoints through Aggressive Lipid Lowering Study), 8888 patsyentov kotoroe included (in vozrastnom bands 26-80 years, 19% women, 99.3% evropeoydnoy rasы representatives, representatives monholoydnoy 0.4% rasы, 0, 3% nehroydnoy rasы representatives and others 0.04%) kotoryya poluchaly lyprymar a dose of 80 mg / day (n = 4439) or a dose simvastatin 20-40 mg per day (n = 4449), was observed not nykakoho often is a total otlychyya nezhelatelnыh reactions or reactions sereznыh nezhelatelnыh Between Groups in techenye of treatment observation period posleduyuscheho with medyanoy prodolzhyt 4.8 UAH Duration, nights year.

In research SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels), kotoroe included patsyenta 4731 (vozrastnoy The range 21-92 years, 40% women, 93.3% evropeoydnoy rasы representatives, representatives nehroydnoy 3.0% rasы 0.6% representatives monholoydnoy rasы and 3.1% others) without vыrazhennoy Clinical yshemycheskoy heart disease, but with availability in anamneze stroke or transient yshemycheskoy attack (TIA) in techenye predыduschyh 6 months, kotoryya poluchaly lyprymar a dose of 80 mg (n = 2365) or placebo (n = 2366) in techenye posleduyuscheho observation period with medyanoy Duration 4.9 year yes, more than nablyudalas Peak time Increase the frequency of cases of sustainable urovnja pechenochnыh transaminases (3 times or more than Above upper boundaries norm Double-bands for 4-10 days) in the group patsyentov, poluchavshyh atorvastatin (0,9%) compared to placebo hruppoy (0.1%). Increase cases urovnja CPK (Above 10 times the upper boundaries norms) bыly rarely, but nablyudalys chashche in the group patsyentov, poluchavshyh atorvastatin (0.1%), than in the placebo group (0.0%). Saharnыy diabetes bыl zarehystryrovan in kachestve nezhelatelnoy reaction patsyentov in 144 (6.1%) in the group, poluchavshey atorvastatin patsyentov and 89 (3.8%) in the placebo group (see. Section "Features Application").

In post-hoc analysis showed something lyprymar a dose of 80 mg umenshal frequency of ischemic stroke (218/2365, 274/2366 against 9.2%, 11.6%) and povыshal frequency of cases of hemorrhagic stroke (55/2365, 2, 3 33/2366% against 1.4%) compared to placebo. The frequency of cases of fatal hemorrhagic stroke bыla podobnoy Between group (17 cases in the group lyprymar drug compared to 18 cases in the placebo group). The frequency of cases of non-lethal hemorrhagic stroke bыla Significantly Above patsyentov in the group, poluchavshyh atorvastatin (38 cases of non-lethal hemorrhagic stroke) compared to placebo hruppoy (16 cases of non-lethal hemorrhagic stroke). Okazalos, something patsyentы, kotoryya take research with hemorrhagic stroke in history,poluchyly povыshennыy risk of hemorrhagic stroke (7 (16%) lyprymar 2 (4%) placebo).

Znachymыh razlychyy Between Groups of treatment for letalnosti patsyentov for reasons not everybody was observed, 216 (9.1%) in the group, poluchavshey lyprymar a dose of 80 mg / day against 211 (8.9%) in the placebo group. Part patsyentov, kotoryya died because of the cardiovascular pathology, bыla numerically less in the group patsyentov, poluchavshyh lyprymar a dose of 80 mg (3.3%), than in the placebo group (4.1%). Part patsyentov, kotoryya died not because of the cardiovascular pathology, bыla numerically bolshe in the group patsyentov, poluchavshyh lyprymar a dose of 80 mg (5.0%), than in the placebo group (4.0%).

Experience postrehystratsyonnыh Application drug.

In techenye postrehystratsyonnыh Application drug lyprymar bыly obnaruzhenы nyzhepryvedennыe Side reactions. Since about эtyh reaction soobschaetsya dobrovolnoy basis for such Unknown Size populyatsyy not always significantly Perhaps Rate s frequency or establish a cause-sledstvennuyu primeneniem connection with the drug.

K nezhelatelnыh reactions svyazannыh with Treatment lyprymar, REGISTERED after Exit drugs on the Marketplace, nezavysymo from otsenki cause and sledstvennoy communication, include reaction: anaphylaxis, anhyonevrotycheskyy edema, bulleznaya sыp (including exudative mnohoformnaya эrytema syndrome, Stevens Johnson and toxic epidermal nekrolyz) , rabdomyolyz, myositis, Fatigue peak times, suhozhylyya gap, and letalnaya neletalnaya pechenochnaya failure, dizziness, depression, peryferycheskaya neuropathy and pancreatitis.

Redkye messages acted on cases immunological mediated necrotizing myopathy, svyazannoy primeneniem with statins (see. Section "Features Application").

Redkye acted postrehystratsyonnыh a message at kohnytyvnыe disorders (for example loss of memory, zabыvchyvost, amnesia, memory violation, sputannost consciousness ) related primeneniem statins. These disorders kohnytyvnыe bыly zarehystryrovanы Application vseh with statins. Otchetы not otnosylys for whole categories sereznыh nezhelatelnыh These reactions and manifestations bыly obratymыmy after prekraschenyya pryema statins, with raznыm of time to beginning of symptom manifestations ( from 1 day to Several years) and yscheznovenyya symptoms (medyana Duration sostavlyala Nedeli 3).

With Application nekotorыh statins bыly opysanы nezhelatelnыe Such phenomena: Sexual function disorders; ysklyuchytelnыe cases of interstitial lung disease, especially t TIME dlytelnoho treatment.

Vaud TIME postmarketynhovыh observations was reported at nyzhepryvedennыe Side reactions.

Violation functions krovenosnoy and lymfatycheskoy system: thrombocytopenia.

Violation functions ymmunnoy system: allerhycheskye reaction, anafilakticheskom shock (including shock anafilakticheskom).

Violation metabolism and POWER: Increase Fire-proof compounds the body.

Violation functions nervous system: Headache pain, hypestezyya, dyshevzyya.

Gastrointestinal tract: pain in vivo.

Violation function of organs of hearing and equilibrium: the noise in the ears.

The skin and podkozhnaya fabric: krapyvnytsa.

Violation functions supporting-dvyhatelnoho apparatus and soedynytelnoy fabric: arthralgia, pain in the back.

Sharing violations, chest pain, edema peryferycheskyy, nedomohanye, fatigue.

Changes laboratornыh analyzov results: Increase alanine-aminotransferase activity, Increase blood CPK activity.

Dety (10-17 years)

Vaud TIME 26-week kontrolyruemoho research in men and in women after the beginning of menstruation (n = 140, 31% zhenskoho floor, 92 representatives evropeoydnoy rasы%, 1.6% nehroydnoy rasы representatives, representatives monholoydnoy 1.6% and 4.8 rasы% эtnycheskyh representatives of the second group), Profil safety and tolerability lyprymar a dose from 10 mg to 20 mg per day as a whole bыl the Profile podobnыm placebo (cm. divisions "Method and Application dozы" "Dety").

Term hodnosty

3 years.

Terms and conditions of storage

Special terms are not trebuyutsya storage. Hranyt out of reach of children place.

Packaging

10 tablets in a blister, 3 kartonnoy blister in the box. For tablets 10 mg and 20 mg

10 tablets in a blister, 3 or 10 blister blysterov in kartonnoy box.

SUBSCRIBE Category otpuska

prescription.


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