Torvazin 10mg Egis drugs for hypercholesterol, prevent cardiovascular disease (3 blisters x 10 tablets)

Atorvastatin reduces cholesterol and lipoprotein levels by inhibiting HMG-COA Reductase and then cholesterol biosynthesis in the liver and increases the number of LDL receptors in the liver on the cell surface that enhances LDL absorption and catabolism.

Atorvastatin reduces the formation of LDL and the number of LDL sub -fertilizers. Atorvastatin creates a complete and sustainable increase in the activity of the LDL receptor along with the beneficial change in the quality of the circulating LDL particles.

Atorvastatin is effective in reducing LDL-C in patients with hypertonic hypertension, patients with patients who often do not respond to lipid lowering drugs.

pharmacokinetic

absorption

Atorvastatin is quickly absorbed after drinking, the peak of plasma (CMAX) is reached within 1 to 2 hours. The level of absorption increases corresponding to the dose of Atorvastatin.

After drinking, Atorvastatin film tablets are 95% to 99% compared to oral solution.

Low body use is due to clearance before absorbing the whole body in the gastrointestinal mucosa and/or initial metabolism in the liver.

Distribution

ATORVASTATIN ABOUT ANIVITIES OF ATORVASTATIN reached approximately 381 liters. There are ≥ 98% Atorvastatin associated with plasma proteins.

Metabolism

Atorvastatin is converted by Cytochrome P450 3A4 into Ortho and ParahydroxyYLization derivatives and different beta-oxygen products. These products are also continued to be transformed through glucuronide. In Vitro, HMG-CoA Reductase inhibitors of Ortho and parahydroxylate metabolites are equivalent to Atorvastatin.

About 70% of HMG-CoA Reductase inhibitors are of active metabolites.

Elimination

Atorvastatin is excreted mainly through bile after the metabolism in the liver and/or outside the liver.

However, Atorvastatin does not participate significantly in the intestinal circulation. The average selling time of Atorvastatin in plasma is approximately 14 hours.

The sale time of HMG-CoA Reductase inhibitors is about 20 to 30 hours due to the participation of active metabolites.

Special patients

Older people

Atorvastatin concentration and higher active plasma metabolites in the elderly are healthy than young people while the effects on lipid are similar to young patients.

Children

According to an 8 -week labeling study, tanner 1 (n = 15) and the tanner stage ≥ 2 (n = 24) Children's patients (aged 6 - 17) increased family -style family cholesterol and initial LDL -C concentration ≥ 4 mmol/l treated with Atorvastatin 5 or 10 mg or 10 mg or 20 mg or 20 mg, every day.

Body weight is only an important half in the PK model of the user atorvastatin.

Atorvastatin's apparent oral clearance in children is similar to adults when comparing by body weight.

Suitable reduction in LDL-C and total cholesterol levels observed throughout the contact range of Atorvastatin and O-Hydroxyatorvastatin.

Gender

Atorvastatin concentration and active metabolites in women are different from men (women: CMAX is approximately 20% higher and AUC is approximately 10% lower).

These differences are not of significant clinical significance, resulting in no clinical significance in the effect of lipids between men and women.

kidney failure

Kidney disease does not affect plasma concentrations or atorvastatin's lipids and active metabolites.

Hepatic failure

Atorvastatin plasma concentrations and metabolites have a significant increase in activity (CMAX increases by approximately 16 times and AUC increases by approximately 11 times) in patients with chronic liver disease due to alcohol (group B).

Simultaneous treatment with other drugs

Increased risk of muscle patterns when Atorvastatin is simultaneously used with drugs that can cause increased Atorvastatin concentration in plasma such as strong inhibitors or CYP3A4 or shipping proteins (for example: Colchicin, Cyclosporin, Telithromycin, Clarithromycin, Delavirdin, Stiripentol, Ketoconone, Ketoconone, Ketoconon, Ketocon, Ketocon, Ketocon Voriconazole, Itraconazole, Posaconazole and HIV and HCV-Protease inhibitors include Ritonavir, Lopinavir, Atazanavir, Indinavir, Darunavir, etc.

Simultaneous use of statin lipid medications with HIV and hepatitis C (HCV) can increase the risk of muscle damage, the most serious muscle, kidney damage leading to kidney failure and may be fatal.

The risk of muscle disease may also increase due to simultaneous use of gemfibrozil and other fibric acid derivatives, erythromycin, niacin and ezetimibe. If possible, it is necessary to consider replacement (non -interactive) therapies instead of these drugs.

In cases where it is necessary to simultaneously use these drugs with Atorvastatin, it is necessary to consider the benefits and risks of treatment. When patients are taking drugs that can increase the concentration of Atorvastatin in plasma, Atorvastatin should be used at a lower dose than the maximum dose.

In addition, when using strong CYP3A4 inhibitors, Atorvastatin is required at a lower starting dose and it is necessary to conduct appropriate clinical monitoring for these patients (see the interaction with other drugs and other forms of interactions).

Do not simultaneously use Atorvastatin and Fusidic acid, so it is important to consider stopping the use of Atorvastatin during the treatment of fusidic acid (see the interaction with other drugs and other forms of interactions).

interstitial lung disease

Some special cases of interstitial lung disease have been recorded when using some statins, especially long -term treatment (see the item of unwanted effects).

The most common manifestation includes shortness of breath, dry cough and general health decline (fatigue, weight loss and fever). If a patient is suspected of interstitial lung disease, statin should be stopped.

diabetes

Some evidence suggests that statins increase blood sugar levels in some patients at high risk of diabetes, causing hyperglycemia, leading to treatment. However, this risk is not significant compared to reducing the cardiovascular risk of statin and therefore it is not the reason to stop treatment with statin.

Patients with risk of hyperglycemia (blood sugar at 5.6 to 6.9 mmol/l, body mass index (BMI)> 30 kg/m2, increased triglycerides, hypertension) should be clinically monitored and biochemical according to national instructions.

Use children's drugs

Safety when using drugs for children has not been determined (see the unwanted effects).

excipients

torvazin contains lactose. Patients with rare genetic diseases cause galactose tolerance, lactase lactase deficiency or glucose-galactose malabsorption should not be taken.

The ability to drive and operate machinery

Torvazin has a significant impact on the ability to drive and operate machinery.

Pregnancy

Do not use Torvazin during pregnancy (see the contraindication section).

The safety of the drug when used for pregnant women has not been determined. There are no clinical trials that control the use of Atorvastatin for pregnant women. There have been rare reports on birth defects after exposure to HMG-CoA Reductase inhibitors in the uterus.

Animal research has shown the toxicity of the drug for reproduction (see the preclinical safety data).

Mother treatment with Atorvastatin can reduce the Mevalonate - a precursor of the fetal cholesterol biosynthesis. Atherosclerosis is a chronic process, and usually stopping lipid lowering drugs during pregnancy will have a small impact on the long -term risks of primary hypercholesterolemia.

For these reasons, Torvazin should not be used for pregnant women, are planning to get pregnant or suspected of being pregnant.

Should temporarily suspend treatment with Torvazin during pregnancy or until determining that a woman is not pregnant (see the contraindications).

Breastfeeding period

It is unknown whether Atorvastatin or its metabolites are secreted into breast milk, in mice, Atorvastatin levels and its metabolites in plasma are similar to the mother mouse milk (see the property data section).

Due to the possibility of serious harmful reactions, women who are taking Torvazin should not breastfeed (see the contraindications).

Atorvastatin is contraindicated during the breastfeeding period (see the contraindications).

Drug interaction

The effect of simultaneous medications on Atorvastatin

Atorvastatin is metabolized by Cytochrome P450 3A4 (CYP3A4) and is a substrate for protein transportation such as transportation absorption at the liver OATP1 B1.

Concentrated use of drugs are inhibitors or substrates (for example, colchicin) of CYP3A4 or transport proteins that can lead to increased plasma Atorvastatin levels and increase the risk of muscle disease.

The risk may also increase when using Atorvastatin simultaneously with other drugs that are likely to cause muscle disease, such as other cholesterol -reducing drugs such as Fibric acid and ezetimibe derivatives (see the warning and caution especially when used).

CYP3A4 inhibitors

Should avoid simultaneous use of powerful CYP3A4 inhibitors (for example: cyclosporin, telithromycin, clarithromycin, delavirdin, stiripentol, ketoconazole, voriconazole, iTraconazole, posaconazole and HIV -Protease inhibitors include Tipranavid + ritonavir, ritonavir, ritonavir + ritonavir + ritonavir + ritonavir Telipravir, etc.) If possible.

In cases where it is impossible to avoid the use of protease inhibitors with Atorvastatin, it is necessary to use caution and should use the lowest atorvastatin doses (Lopanavir + Ritonavir) or use no more than 40 mg Atorvastatin/day (NELFINAVIR) or no more than 20mg/day (Darunavir + Ritonavir, Fosamprenreniren, Fosamprenrenavir, Fosamprenrenavir, Fosamprenrenavir, Fosampren Fosamprenavir + Ritonavir, Saquinavir + Ritonavir) (see Table 1).

Average CYP3A4 inhibitors (such as erythromycin, diltiazem, verapamil and fluconazole) may increase the concentration of Atorvastatin in plasma (see Table 1).

Increased muscle disease risk has been recorded when using erythromycin simultaneously with statins. Research on drug interaction assessment of the effect of Amiodaron or Verapamil to Atorvastatin has not been conducted.

Both Amiodaron and Verapamil are known to inhibit the activity of CYP3A4 and when simultaneously used with Atorvastatin can cause increased contact with Atorvastatin. Therefore, Atorvastatin should be considered at a lower dosage and a clinical monitoring is suitable for patients to use Atorvastatin simultaneously with average CYP3A4 inhibitors.

It is necessary to follow the appropriate clinical monitoring after starting or after adjusting the CYP3A4 inhibitors.

CYP3A4 induction substance

Due to the dual interaction mechanism of Rifampin (Cytochrome P450 3A touch and inhibit the QatP1B1 liver cell absorption agent, it is recommended to simultaneously use Atorvastatin with rifampin, because using Atorvastatin after using Rifampin significantly reduces Atorvastatin concentration in plasma.

However, the effect of rifampin on Atorvastatin concentration in liver cells has not been known and if it is not possible to avoid simultaneous use, it is necessary to monitor patients carefully to control the effectiveness of treatment.

Transport protein inhibitors

Transport protein inhibitors (e.g. cyclosporin) may increase the body contact level of Atorvastatin (see Table 1).

The effect of inhibitors of the liver absorption substances on the Atorvastatin concentration in unknown liver cells.

If it is impossible to avoid using these drugs, the dose should be reduced and clinically monitored to control the effectiveness of treatment (see Table 1).

gemfibrozil/derivative of fibric acid

The use of solitary fibrats sometimes related to mechanical events, including muscle pattern.

The risk of these events can be increased by simultaneous use of fibric acid and atorvastatin.

If it is unavoidable to simultaneously use these drugs, the lowest atorvastatin dose should be used to achieve the purpose of treatment and need to monitor the patient appropriately (see the warning and prudence especially when used).

ezetimibe

The use of solitary ezetimibe can cause muscle -related events, including muscle pattern. The risk of these events can be increased by simultaneous use of Ezetimibe and Atorvastatin. Clinical monitoring is required for these patients.

Colestipol

Atorvastatin concentration in plasma and lower activity metabolites (approximately 25%) when using Colestipol simultaneously with Atorvastatin.

However, the lipid reduction effect is greater when using Atorvastatin and Colestipol compared to one of these two lonely drugs.

Fusidic acid

Studies on interaction with Atorvastatin and Fusidic acid have not been conducted. As with other statins, muscle -related events, including muscle pattern, have been reported during the circulation of drugs when used simultaneously atorvastatin and fusidic acid. The mechanism of this interaction is not known.

Need to monitor patient closely and may consider stopping treatment with atorvastatin.

niacin

The risk of unwanted effects on skeletal muscles increases when using atorvastatin simultaneously with niacin, it is necessary to consider reducing the dose of Atorvastatin in this case (see the warning and special cautious part when used).

diltiazem

diltiazem increases the level of Atorvastatin in plasma, increasing the risk of muscle pattern and kidney failure.

The influence of Atorvastatin on other drugs is simultaneously used

digoxin

When using simultaneously, the dose repeats digoxin and 10 mg atorvastatin, the concentration of digoxin in a stable state increases slightly. Need to monitor patients who are using Digoxin appropriately.

Oral contraceptive pills

Simultaneous use of Atorvastatin with oral contraceptives increases the concentration of norethindrone and ethinyl oestradiol in plasma.

warfarin

In a clinical study in patients using prolonged warfarin, simultaneous use of Atorvastatin 80 mg daily with warfarin causes mitigating prothrombin time about 1.7 seconds in the first 4 days of medication, this condition returns to normal within 15 days of Atorvastatin treatment.

Although there are only rare cases of interactive cases with anticoagulants are significant clinical significance, prothrombin should be determined before starting atorvastatin treatment in patients with Coumarin anticoagulants and periodically during the beginning of the treatment process to ensure significant prothrombin time.

As soon as the prothrombin time is stable, prothrombin can be monitored over time, which is often recommended for patients who are taking coumarin anticoagulants.

If the dose changes or stopping Atorvastatin, it is necessary to repeat the same process. Atorvastatin is not related to bleeding or changing prothrombin time in patients without anticoagulants.

Bile acid -mounted resins

Bile acid -mounted resins (for example, Cholestyramin, Colestipol) can significantly reduce the bioavailability of statin when taken together. So the time to use these 2 drugs must be apart.

Although there is no clinical interactive studies in clinical interactions, there is no clinical interactive manifestation of clinical significance when using statin along with angiotensin transferring enzymes, beta blockers, calcium channel blockers, diuretics and nonsteroidal anti -inflammatory drugs.

Table 1: Effect of simultaneously used drugs on atorvastatin pharmacokinetics