Insuation 10 Savi Pharm reduces total cholesterol levels (3 blisters x 10 tablets)

There are 2 or more cardiovascular risk factors.

Preventive cardiovascular events.

pharmacokinetic

absorption

Atorvastatin is quickly absorbed after taken, the maximum plasma drug concentration is achieved within 1-2 hours. The level of absorption and concentration of Atorvastatin increases proportional to the dosage of Atorvastatin. Atorvastatin tablet form is 95 - 99% of the solution.

Plasma Atorvastatin concentrations after taking the evening in the evening are lower in the morning when used in the morning (about 30% for CMAX and AUC). However, the effectiveness of LDL-C reduction is the same regardless of the time when taking the drug during the day (see the dose).

distribution

The average distribution of Atorvastatin is about 381 liters. Over 98% of Atorvastatin is connected to plasma proteins. The ratio of plasma red blood cells is approximately 0.25, showing the permeability into low red blood cells.

transformation

Atorvastatin is converted mainly into hydroxylation derivatives at Ortho and Para positions and oxidation products at beta. In vitro, the inhibition of the HMG-CoA reducing enzyme of metabolic substances through the hydroxylation pathway in the Ortho and Para position is equivalent to the inhibition of Atorvastatin.

About 70% of the plasma inhibitors of HMG-CAA enzymes are caused by active metabolites. In vitro, studies show the importance of Atorvastatin metabolism by Cytochrom P450 3A4 liver, suitable for the concentration of Atorvastatin in plasma increases in humans after simultaneous use with Erythromycin, a known inhibitor of this Isozym (see carefully when used and drug interactions). In animals, the metabolites of ortho-hydroxy will undergo more glucuronide.

Elimination

Atorvastatin and its metabolites are excreted mainly through bile after the metabolism in the liver and/or outside the liver. However, the drug does not go through the gut liver cycle.

The semi -cancellation time in the average plasma of Atorvastatin in humans is about 14 hours, but half of the time of HMG -CAA reducing enzyme inhibitors is 10-20 hours due to the contribution of active metabolites. Under 2% of the oral atorvastatin is found in the urine.

Special patient groups

Elderly

Atorvastatin concentration in plasma in older, healthy (

Children

In the 8 -week study Tanner Stage ≥ 2 in children (from 6 - 17 years old) increased the heterozygous family blood cholesterol with LDL -C ≥ 4 mmol/l treated with Atorvastatin 10 or 20 mg/time/day showing that body weight has a great influence on the dynamic index of Atorvastatin in children. Atorvastatin's clearance in children is similar to adults after weight calibration. The decrease in LDL-C and total cholesterol has been observed corresponding to the increase in AUC of Atorvastatin and Ortho-Hydroxyatorvastatin.

Gender

Atorvastatin concentration in plasma in women is different from men (about 20% higher than CMAX and about 10% lower for AUC). However, there is no clinical difference in clinical effect on the effectiveness of treatment on blood lipids between men and women.

kidney failure

Kidney pathology does not affect the concentration of drugs in plasma or treatment effects of Atorvastatin. Therefore, it is not necessary to adjust the dosage in patients with renal impairment (see the dose and usage).

Hemorrhage

Although studies have not been conducted in end -stage renal failure patients, hemorrhage has no hope to significantly increase the clearance of Atorvastatin because the drug is strongly connected to plasma proteins.

Hepatic failure

Atorvastatin concentration in plasma increases significantly in patients with chronic liver disease due to alcohol, about 16 times for CMAX and 11 times for AUC (see contraindicated).

Sloc1b1 polymorphic polymorphism

HMG-CoA Reductase inhibitors are transported into the liver by CATP1B1 transport protein. In patients with SLCO1B1 polymorphic genes, they are at risk of increasing Atorvastatin levels, which can lead to increased risk of muscle pattern. Oatp1B1 encryption gene (SLCO11B1 c. 521cc) is related to the increase of AUC 2.5 times higher than people without this genotype (c. 521tt). Reducing the absorption in the liver due to genetics can also occur in these patients. The consequences are not well known.

Be cautious when using clinical lipid medications with HIV and hepatitis C (HCV) because it may increase the risk of muscle damage, the most serious pattern, kidney damage leads to kidney failure and can be fatal.

Endocrine

HBA1C increases and hungry blood sugar have been reported with HMG-COA inhibitors, including Atorvastatin.

Statin affects cholesterol synthesis and theoretically can reduce the production of steroids in the adrenal gland. Clinical studies show that Atorvastatin does not affect the level of cortisol in the body and reserves in the adrenal gland. The effect of Atorvastatin on male fertility has not been studied on the appropriate number of patients. The effects on the pituitary -genitals in women have not been evaluated.

Be cautious when using statins simultaneously with drugs that reduce endogenous hormone secretion activities such as ketoconazol, spironolacton and cimetidine.

diabetes

Some evidence suggests that statin increases blood sugar in some patients, increasing the risk of future diabetes. However, statin should not be stopped for the benefit of reducing cardiovascular risk due to statin, which is greater than the risk of hyperglycemia. Patients are at high risk (5.6 - 6.9 mmol, BMI> 30 kg/m, hypertension, hypertension, triglycerides) should be closely monitored and subclinical.

Central nervous toxicity

Cerebral hemorrhage has been observed in an individual dog treated for 3 months at a dose of 120mg/kg/day. The dose of 120mg/kg/day causes an increase in AUC about 16 times compared to the dose of 80mg/day in humans. Cerebral hemorrhage and optic neurological degeneration have been observed in other female dogs in a state of dying after 11 weeks of treatment with increasing dose to 280mg/kg/day.

In a 2 -year study, observing convulsions in two male dogs. No nerve damage in the mouse is not seen when treated within 2 years with a dose of up to 400mg/kg/day.

Prevention of stroke by sharply reducing cholesterol levels (SparCl)

stroke prevention by aggressive reduction in cholesterol levels): In the analysis after experiments related to stroke, patients without coronary artery disease recently or with transient brain anemia, Atorvastatin 80mg users have a higher hemorrhagic stroke rate, compared to placebo.

The risk of an increase in people with a history of hemorrhagic stroke or hole infarction. For patients with a history of hemorrhagic stroke or defect infarction, the benefits and risks of using Atorvastatin 80mg have not been assessed firmly and should consider the risk of hemorrhagic stroke at the beginning of treatment.

Interstitial lung disease

has been reported in some statins, especially when used for prolonged use. Symptoms include: shortness of breath, dry cough and health impairment (fatigue, weight loss and fever). If the patient is suspected of developing interstitial lung disease, the drug should be stopped immediately.

The ability to drive and operate machinery

Atorvastatin does not affect the ability to drive and operate machinery.

Pregnancy

Contraindicated Insuat 10mg Savi 3x10 in pregnant women. Safety has not been set in pregnant women. There are no clinical trials that have been performed in pregnant women. There have been rare reports on fetal birth defects after exposure to HMC-CoA Reductase inhibitors in the uterus. Animal studies have shown reproductive toxicity.

Mothers using Atorvastatin may reduce the fetal meevalonate level, which is a pre -synthetic precursor cholesterol. Atherosclerosis is a chronic, prolonged process, so the stopping of using lipid medication during pregnancy has a little impact on the long -term risk of hypercholesterolic hypercoles.

For these reasons, do not use Insuat 10mg Savi 3x10 in pregnant women, are planning to get pregnant or suspected of being pregnant. It is recommended to stop insuat 10mg Savi 3x10 during pregnancy or until it is determined not to be pregnant.

Women of reproductive age should use appropriate contraception while being treated with Atorvastatin.

Breastfeeding period

It is unknown whether Atorvastatin and its metabolites will be secreted into human milk. In mice, Atorvastatin concentrations and metabolites are active in milk equivalent to plasma concentrations. Due to the potential of serious side effects, breastfeeding should not be breastfeeding when using Insuat 10mg Savi 3x10. Atorvastatin contraindicated during breastfeeding.

In animal studies, Atorvastatin does not affect fertility in both men and women.

Drug interaction

The effect of other drugs on Atorvastatin

Atorvastatin is metabolized by cytochrom P450 3A4 and is a substrate of transport proteins. Concentrated use of CYP 3A4 inhibitors or shipping proteins may increase Atorvastatin levels and increase muscle disease risk. The risk also increases when using Atorvastatin simultaneously with other drugs that are likely to cause muscle disease such as the derivatives of fibric acid and ezetimib.

CYP3A4 inhibitors

Strong CYP3A4 inhibitors cause significant increase in Atorvastatin levels. The coordination of strong CYP3A4 inhibitors (such as Ciclosporin, Telithromycin, Clarithromycin, Delavirdin, Stiripentol, Ketoconazol, Voricazol, Itraconazol, Posaconazol and HIV Ritonavir, Lopinavir, Lopinavir, actazanavir, indomavir, indomavir, indomavir, indomavir, indomavir, indoma Darunavir, ...). In case of compulsory use, it is advisable to consider the starting dose, the maximum dose appropriately and closely monitor patients.

medium inhibitors CYP3A4 (erythromycin, diltiazem, verapamil and fluconazole) may increase the plasma concentration of Atorvastatin. The risk of increased muscle disease has been observed when used in combination with erythromycin and statin. Researching and assessing the interaction of Amiodaron or Verapamil on Atorvastatin has not been done. Amiodaron and Verapamil are known to inhibit CYP3A4 and the same use with Atorvastatin can cause increased Atorvastatin levels. Therefore, it is necessary to consider lowering atorvastatin doses and should monitor patients closely when used in combination with CYP3A4 inhibitors. Clinical monitoring should be appropriate after starting or after each adjustment of the inhibitors.

CYP3A4 induction

Use atorvastatin combination with CYP3A4 touch substances (Efavirenz, Rifampin, St. John's Wort) may reduce the level of Atorvastatin in plasma. Due to the double interactive mechanism of Rifampin (P450 3A touch and inhibit the transport protein absorption of OATP1B1 liver), the sharing of Atorvastatin and Rifampin is recommended, because the time of taking atorvastatin oral time after drinking Rifampin causes reduced Atorvastatin concentration. However, it is unknown the effect of rifampin on Atorvastatin's concentration in liver cells, so if they have to be shared, patients need to be carefully monitored about the effectiveness of the drug.

Transport protein inhibitors

Transport protein inhibitors (such as ciclosporin) may increase Atorvastatin levels. It is unknown the effect of the inhibitor of transportation protein absorption in the liver on the concentration of Atorvastatin in liver cells. If shared, dose should be reduced and monitor patients carefully.

gemfibrozil/Fibric acid leading

The solitary use of fibrats is related to side effects, including pattern. Increased risk when used with Atorvastatin. If this combination must be used, the lowest dose of Atorvastatin should be used and need to monitor the patient appropriately.

ezetimib

Ezetimib also causes side effects, including muscle pattern. Therefore, the risk of side effects on muscle will increase when used in combination with ezetimib with Atorvastatin. Should follow the appropriate patient.

Colestipol

When used with Colestipol, Atorvastatin's concentration and its metabolites are reduced. However, when using this combination, the effect of lowering blood lipids increases compared to when using each single drug.

cholestyramin

Atorvastatin concentration in plasma decreases (about 25%) when using cholestyramin along with Atorvastatin. However, the effectiveness of treatment on blood lipids when using 2 drugs is higher when only 1 of 2 drugs.

Fusidic acid

The risk of muscle disease, including muscle pepper, can still increase when sharing fusidic acid with statin. The mechanism of this interaction has not been clarified. There have been reports on cases of muscle pattern (some deaths) when using this combination. Atorvastatin should be stopped during treatment with fusidic acid.

colchicin

Although the drug interaction between Atorvastatin and Colchicin has not been studied, there have been reports of some muscle lesions when used in this combination. Therefore, it is necessary to be cautious when indicated for the patient to use this combination.

antacid

Simultaneous use of Atorvastatin with oral antacid contains magnesium and aluminum hydroxyd, which will reduce the level of Atorvastatin in plasma by about 35%, however, the effect of the drug on the effectiveness of LDL-C reduction is not changed.

Pomelo juice

Using pressed grapefruit juice (there are many ingredients inhibiting CYP 3A4) with Atorvastatin may increase the concentration of drugs in the blood.

niacin

The risk of side effects may increase when using atorvastatin with niacin, should consider reducing Atorvastatin in this case.

The influence of Atorvastatin on other drugs

digoxin

Simultaneous use of Atorvastatin and Digoxin increases plasma digoxin concentrations in a stable state of nearly 20%. Appropriate monitoring of patients who are using digoxin.

Oral contraceptives

Concentrated with oral contraceptive pill contains Norethindron and Ethinyl Estradiol increases the AUC of Norethindron and of Ethinyl Estradiol nearly 20%. When choosing contraceptives for women who are taking Atorvastatin should consider this.

warfarin

In the clinical research in patients with long -term warfarin therapy, the combination of Atorvastatin 80mg daily with warfarin reduces PT (prothrombin time) by about 1.7 seconds during the first 4 days and returns to normal after 15 days of treatment with Atorvastatin.

Once the face is very rare for drug interaction with anticoagulant drugs, PT should also be checked before taking Atorvastatin in patients who are taking anticoagulants and should be monitored regularly during the early stages of the treatment process to ensure no major changes in PT. When PT has stabilized, patients taking anticoagulants are recommended to monitor PT periodically. If the dose changes or stops atorvastatin, this process is needed. Atorvastatin is known not to bleed or change PT in non -anticoagulants.

Other drugs

In clinical studies, when concurrent Atorvastatin with antihypertensive drugs and estrogen replacement therapy, there is no clinical adverse drug interaction.