Pastetra Pharbaco prevents cardiovascular diseases, hypercholesterol (3 blisters x 10 tablets)

Pastetra is indicated as a supportive therapy for diet in patients with hypercholesteroline hypercholesterol patients with homozygous family. Patients may also receive supportive treatments (eg plasma filtering LDL).

Pharmacokology

Atorvastatin:

Pharmacological effects: Blood lipid regulator, HMG-COA Reductase inhibitors.

ATC: C10AA05.

Atorvastatin belongs to the statin group is the lipid air conditioner group. Statin is also known as HMG-Coa Reductase inhibitors because of the competitive inhibitor with HMG-COA Reductase, is the HMG-CAA conversion catalyst into Mevalonic Acid, a premature precursor of cholesterol.

Atorvastatin reduces cholesterol and plasma lipoprotein by inhibiting HMG-COA Reductase reduction enzymes and cholesterol synthesis in the liver and by increasing the number of LDL-C receptors in the liver on the surface cell to increase the recovery and metabolism of LDL-C.

Atorvastatin reduces the production of LDL-C and the number of LDL-C sub-fertilizers. In patients with hypercholester hyperchemical hyperplopathy and heterozygous, blood cholesterol hyperplasia, and mixed blood lipid disorders, Atorvastatin reduces partial parts, LDL-C, and APO B. Atorvastatin also reduce lipoprotein cholesterol (VLDL-C) and Triglyceride and HDL-C in HDL-C in HDL-C in HDL-C in HDL-C in HDL-C in HDL-C in HDL-C in HDL-C in HDL-C in HDL-C in HDL-C in HDL- Tuong.

Atorvastatin increases and maintains the activity of LDL receptors accompanied by beneficial changes in the quality of the circulating LDL-C sub-fertilizers. Atorvastatin is effective in reducing LDL-C in patients with hypercholesteroline hypercholesterol, homozygous family, subject groups often do not respond to lipid medications.

In a dose-response evaluation study showed that Atorvastatin reduced total cholesterol (30%-46%), LDL-C (41%-61%), apolipoprotein B (34%-50%) and triglycerides (14%-33%). These results maintain stable in patients with hyperlemed hyperlemor hyperplastic hyperplasia, non -family hypercholesteroline hyperplasia and mixed hyperlipidemia, including insulin -dependent diabetes patients.

To reduce total cholesterol, LDL-C, Apolipoprotein B has been shown to reduce the risk of cardiovascular events and cardiovascular death.

In addition, statin also has anti -atherosclerotic effects. Most have proved to slow down the process of progress and or retreat atherosclerosis and/or carotid arteries. The current mechanism of action is unknown, but this effect can be independent of the effect of regulating blood lipids.

Hydrand -lowering effect: Statin reduces blood pressure in people with hypertension and hyperglycemia. The effect of reducing blood pressure may be associated with the restoration of the endothelial disorder due to statin, activating the endothelial oxygen oxygen and reducing plasma aldosteron levels.

Anti -inflammatory effects: In people with hypercholesteroline hypertension or no coronary artery disease shows that statins may have anti -inflammatory activity. Statin therapy in these patients reduces the CRP plasma (C-Reactive protein) plasma concentrations. CRP levels also decrease in patients with normal cholesterol with high CRP levels before treatment. Effects for CRP levels are not correlated with changing LDL-C levels. Recent studies show that reducing CRP levels may reduce the risk of recurrent myocardial infarction or death from coronary artery causes.

Effect for bones: Statin can increase bone density.

ezetimibe:

Pharmacological effect group: Pipid regulator.

ATC: C10AX09.

Ezetimibe inhibits cholesterol absorption from the intestine. Ezetimibe works when used orally and has mechanisms that are different from the cholesterol -reducing drugs of other groups (such as statins, bile acid secretion inhibitors [resin], fibric acid derivatives, and stanols of plant origin).

The target molecule of Ezetimibe is the molecule of sterol, niiemann-pick C1-Like 1 (NPC1L1), responsible for absorbing cholesterol and phytosterol from the intestine.

Ezetimibe localized at the brush edge of the small intestine and inhibit cholesterol absorption, resulting in reduced cholesterol transportation from the intestine into the liver; Statines reduce cholesterol synthesis in the liver and these two separate mechanisms complement each other to reduce cholesterol.

In a 2 -week clinical study on 18 patients with hypercholesterolemia, Ezetimibe inhibits the absorption of cholesterol in the intestine about 54% compared to Placebo.

A series of clinical studies have been conducted to determine the inhibition of selective cholesterol absorption of Ezetimibe. Ezetimibe inhibits absorption [14C] -cholesterol without affecting the absorption of triglycerides, fatty acids, bile acids, progesterone, ethinylingiol, or vitamins A and D in fat.

In clinical studies, Ezetimibe in combination with statins significantly reduces cholesterol, LDL-C, Apolipoprotein B (APO B) and triglycerides (TG) and HDL-C hyperplasia in hypercholesterol patients.

Dynamic pharmacokinetics

atorvastatin:

absorption:

Atorvastatin is quickly absorbed after drinking and strongly transforming in the liver, the peak concentration of plasma is reached within 1 to 2 hours. The level of absorption and concentration of Atorvastatin in plasma increases proportional to the dose of Atorvastatin. Atorvastatin tablets for bioavailability equal to 95% to 99% of the solution form. The absolute bioavailability of Atorvastatin is approximately 14% and the whole body uses for HMG-CAA reduction inhibition activity is approximately 30%. Low -body bioavailability is due to the clearance of the gastrointestinal mucosa and/or the first metabolism through the liver before the common circulation.

Food changes the bioavailability of Atorvastatin after drinking. Food reduces the speed and/ or absorption level, but due to low reduction, it does not change the clinical change in the effect of regulating blood lipids.

Plasma concentrations after taking Atorvastatin may be related to day and night: Take Atorvastatin in the evening makes the top concentration of the drug in plasma and the area under the concentration - time curve (AUC) decreased by 30 - 60%. Despite reduced bioavailability, Atorvastatin's blood lipid regulation effects in the evening do not change and slightly higher than drinking in the morning.

For the elderly, aged 65 and older, the plasma concentration of Atorvastatin may be higher than the young but does not change the effect of regulating blood lipid.

distribution:

The average distribution volume of Atorvastatin is approximately 381 liters.

The ratio of cohesion with the plasma protein of Atorvastatin ≥ 98%.

Atorvastatin can be through the placenta and distributed into breast milk.

transformation:

Atorvastatin is converted mainly into hydroxy derivatives at Ortho and Para positions and products of oxidation in beta. On Vitro, the HMG-COA reducing enzyme inhibitors of hydroxy metabolites in Ortho and Para are equivalent to this effect of Atorvastatin. Approximately 70% of the inhibition activity in the circulation for HMG-CoA reducing enzymes is due to active metabolites.

excretion:

Atorvastatin and its metabolites are excreted mainly after bile after being metabolized in the liver and/or outside the liver; However, the drug does not seem to have a cycle of re -circulating the gut. The average selling time in Atorvastatin's plasma is approximately 14 hours, but the sale time of the inhibitory activity for HMG-CAA reducing enzymes is 20-30 hours due to the contribution of active metabolites.

Special object group:

Elderly: Atorvastatin concentration in plasma in elderly subjects (≥ 65 years old) is healthy is higher (approximately 40% for CMAX and 30% for AUC) compared to young people.

Sex: Atorvastatin concentration in plasma in other women (higher than approximately 20% for C and lower 10% for AUC) compared to men. However, there is no clinical difference in action on lipid between men and women.

Renal failure: Kidney disease does not have an effect on plasma concentrations or acting on lipids of Atorvastatin. Therefore, it is not necessary to adjust the dose in patients with renal failure.

Hepatic failure: Atorvastatin's plasma concentrations are significantly increased (approximately 16 times for CMAX and 11 times for AUC) in patients with chronic liver disease due to drinking alcohol (type B type).

ezetimibe:

absorption:

After drinking, Ezetimibe is absorbed quickly and strongly into a substance that has the effect of Phenolic Glucuronid (Ezetimibe-Glucuronid). Maximum maximum plasma concentration (CMAX) appears about 1 to 2 hours for Ezetimibe-Glucuronid and 4 to 12 hours for Ezetimibe. Ezetimibe's absolute bioavailability is not determined because this active ingredient does not soluble in the solvent for injection.

Use the same food (high -fat or non -fat meals) does not affect the ezetimibe oral bioavailability.

distribution:

Ezetimibe and Ezetimibe-glucuronid linked to plasma proteins are 99.7% and 88 to 92% respectively.

transformation:

Ezetimibe is basically metabolized in the small intestine and liver thanks to a conjugated with glucuronid (stage II reaction) and then excreted through bile. Minimum oxidation metabolism (stage I reaction) in all species of research.

Ezetimibe and Ezetimibe-Glucuronid are the main metabolic components of the drug determined in plasma, accounting for about 10 to 20% and 80 to 90% of the total number of drugs in plasma. Ezetimibe and Ezetimibe-Glucuronid are eliminated from plasma slowly with significant reuse signs in the gut. Half-life elimination of Ezetimibe and Ezetimibe-Glucuronid about 22 hours.

excretion:

In humans, after taking 14C-Ezetimibe (20 mg), the total ezetimibe accounts for about 93% of the total active ingredient marking radioactive in plasma. The corresponding 78% and 11% of the active ingredient marks the radioactive and urine for 10 days. After 48 hours, no active ingredient marks radioactive in plasma.

Special subject group:

Elderly patients:

The plasma concentration of total ezetimibe in the elderly (> 65 years) is about 2 times higher than the young (18 to 45 years old). LDL-C reduction and safety data in the elderly are equivalent to young people using ezetimibe.

Hepatic failure:

After a single dose of 10 mg Ezetimibe, the area under the curve (AUC) of the total average Ezetimibe increases about 1.7 times in patients with mild liver failure (Child-Pugh 5 or 6) compared to healthy people. In a multi-dose study, lasting 14 days (10 mg per day) in medium liver failure patients (Child-Pugh score from 7 to 9), the average AUC of the total amount of ezetimibe increased about 4 times on day 1 and 14 days compared to healthy people. No dose adjustment in patients with mild liver failure. Ezetimibe should not be used for patients with severe to severe liver impairment (Child-Pugh> 9) due to the unknown effect of increased body concentration of body in these patients.

kidney failure:

After a single dose of 10 mg Ezetimibe in patients with severe hepatic impairment (n = 8; average CrCl ≤ 30 ml/min/1.73m), the average AUC of the total ezetimibe increases about 1.5 times compared to healthy people (n = 9).

A patient in this study (after kidney transplant and many drugs, including cyclosporin), has a whole body concentration of total ezetimibe 12 times higher.

Be cautious when using

need to be very careful when taking the drug for patients in the following cases:

Before and during treatment with pastetra, it is recommended to combine blood cholesterol control by measures such as diet, weight loss, exercise, and treatment of diseases that may be the cause of lipid growth. Periodic lipid quantification and dosage adjustment according to the patient's response to the drug. The goal of treatment is to reduce LDL-C, so it is necessary to use LDL-C levels to start treatment and evaluate treatment. Only when the LDL-C cannot be tested, the total cholesterol uses to monitor treatment.

influence on the liver:

atorvastatin:

In clinical trials, about 0.7% of patients using Atorvastatin see significantly increasing serum transaminase (> 3 normal limits). When stopping the drug in these patients, Transaminase concentration often lowered to the level before treatment. A few of these patients before treatment with statins have abnormal liver function test results and/or drink plenty of alcohol.

ezetimibe:

In clinical studies, the increase in serum transaminase (> 3 normal limits) is 0.5% for ezetimibe and 0.3% for placebo.

In clinical studies, in patients using Ezetimibe combination with Atorvastatin, the ratio of serum transaminase increases (> 3 normal limits) is 0.6%. There are no specific symptoms when increasing transaminase, not related to cholestasis, transaminase concentrations often lower slowly returning to normal when stopping the drug.

The liver enzyme test should be tested before starting to use pastetra and then only redo when the clinical is indicated (such as the suggested manifestations with liver damage). Should be careful in patients with increased serum transaminase levels, and in these patients, the test should be repeated right away and then conduct a more frequent test. The drug should be stopped if the transaminase concentration increases, especially when increasing to 3 times the upper limit of normal and prolonged. Atorvastatin can cause increased transaminase.

There have been a number of rare reports on liver failure and death in patients taking statin. If there is serious liver damage with clinical signs and/or increase blood or jaundice bilirubin during treatment with pastetra, it is necessary to stop the treatment process. If there is no other cause, no further treatment with Pastetra.

Be careful when using pastetra in patients who drink a lot of alcohol and/or have a history of liver disease. Contraindicated to use Atorvastatin for patients with progressive liver disease or persistent transaminase increased.

Due to the unknown effect of increased ezetimibe concentration in patients with average or severe hepatic impairment, Pastetra should not be used for these patients.

Surgery effects:

atorvastatin:

Heavy or fatal patterns have occurred with all rare statins. Quantifying the concentration of Creatine Kinase (CK) Serum before starting Statin therapy is recommended by some experts, especially for patients with high risk of muscle and muscle toxicity (elderly, black skin, users in combination with muscle poison, impaired kidney function, hypothyroidism) to help diagnose muscle disease in patients later have side effects; However, it is not recommended for regular supervisors of serum CK when there is no clinical manifestation.

As well as other HMG-COA reducing enzymes inhibitors, Atorvastatin sometimes causes muscle diseases manifested by muscle pain, muscle tension or muscle weakness, which can progress to muscle pattern. If CK exceeds 10 times the above limit of normal levels can be life -threatening. Myoglobinuria can lead to renal failure.

There have been reports but very rare for muscle necrosis due to immunity (IMNM), an autoimmune muscle disease, related to the use of statin. IMNM is manifested by muscle weakness and increased serum creatine kinase, which continues to exist after stopping the statin.

It is necessary to consider when using Atorvastatin for patients with risk factors leading to muscle damage. Creatin phosphokinase (CPK) should be tested before treatment in the following cases:

Oatp1b1 inhibitors (cyclosporin):

Should avoid pastetra treatment.

clarithromycin, iTraconazole:

Be cautious when the pastetra dose exceeds 20/10mg when used simultaneously with Clarithromycin (500mg, 2 times/day) or Itraconazole 200mg.

grapefruit juice:

contains one or more CYP 3A4 inhibitors and can increase the concentration of Atorvastatin in plasma, especially when drinking too much grapefruit juice (> 1.2 liters/day).

Other interactions:

antacids:

Atorvastatin: Concomitant use with antacids containing magnesi and aluminum hydroxyd, plasma concentrations of Atorvastatin are reduced by about 35%. However, the effect of reducing cholesterol low molecular weight does not change.

Ezetimibe: When using the same antacids, the absorption rate of Ezetimibe decreases but does not affect the bioavailability of ezetimibe. The reduction of this absorption rate is considered without clinical significance.

Bile acid -splitting drugs: Pastetra should be taken away from 2 hours or after 4 hours.

Colestipol: Atorvastatin concentration in plasma decreased by about 25% when used simultaneously Colestipol with Atorvastatin. However, the LDL-C decrease is greater when Atorvastatin and Colestipol are used simultaneously compared to when used for each single drug.

Cholestyramin: Concomitance with Cholestyramin reduces about 55% of Ezetimibe's AUC.

fenofibrat: Due to the risk of muscle disease while treating with HMG-CoA Reductase inhibitors increased when used simultaneously with fenofibrat, pastetra should be used carefully when used simultaneously with fenofibrat.

If gallstones are suspected in patients being treated with pastetra and fenofibrat, they need to study gallbladder and should consider treating other lipids.

In a pharmacokinetic study, simultaneously used with Fenofibrat increases the total ezetimibe level about 1.5 times. This increase is not considered clinical significance.

Avoid simultaneous use of pastetra with the following drugs:

gemfibrozil: Due to an increased risk of muscle disease/muscle pilot when using HMG-Coa Reductase inhibitors with Gemfibrozil, it is advisable to avoid using pastetra with Gemfibrozil.

Other fibrats: The safety and effectiveness of ezetimibe are used with other fibrats that have not been determined. Fibrat can increase cholesterol secretion into bile, leading to gallstones. In a clinical study in dogs, Ezetimibe increases cholesterol in the gallbladder. Although the meaning of this preclinical discovery is unknown to people, simultaneously using pastetra with other fibrats is not recommended until the use in patients is studied.

Fusidic acid: The risk of muscle disease/muscle pattern may increase when using fusidic acid simultaneously and the statins can increase the concentration of plasma of both agents, the mechanism of this interaction is unclear. Although studies on interactive atorvastatin and fusidic acid have not been conducted, there has been a report on serious muscle problems such as the muscle lying when using atorvastatin and Fusidic acid after the drug circulating in the market.

Breast cancer protein inhibitors (BCRP): Elbasvir and Grazoprevir. Atorvastatin is a substrate of the transportation system to BCRP, simultaneously used with Elbasvir and Grazoprevir may increase the level of Atorvastatin in plasma by 1.9 times due to CYP3A and/or BCRP inhibitors and increase the risk of muscle disease; Pastetra should not exceed 20/10mg/day.

anticoagulants:

Atorvastatin: There is no significant influence on prothrombin time when used for patients being treated with long -term warfarin.

Ezetimibe: In a study with 12 mature and healthy men, they found that Ezetimbe simultaneously (10 mg once a day) and the single dose Warfarin did not significantly affect the bioavailability and prothrombin time of Warfarin.

Cytochrom P450 3A4 induction drugs: simultaneous use of Atorvastatin with drugs that cause Cytochrom P450 3A4 (eg Efavirenz, Rifampin) can lead to reduced changes in Atorvastatin concentration in plasma. Due to the double interactive mechanism of rifampin, the same as simultaneous use of Atorvastatin with rifampin because of the late use of Atorvastatin after using Rifampin is associated with a significant reduction in the level of Atorvastatin in plasma.

Antyrin: Because Atorvastatin does not affect the pharmacokinetics of antipipin, interacting with other drugs that are transformed through this iszyme cytochrom is not expected.

Digoxin: When simultaneously use many doses of Atorvastatin and Digoxin, the concentration of digoxin in a stable state increases to about 20%. Patients who are using digoxin should be monitored appropriately.

Oral contraceptives: simultaneously taking Atorvastatin with an oral contraceptive that increases the AUC value of Norethindron and EthinyleLestradiol about 30% and 20%. It is necessary to consider this increase when choosing oral contraceptive pills for a woman being treated with pastetra.

Amlodipin: In a study of drug-medication interaction in healthy subjects, simultaneously used atorvastatin 80mg and amlodipin 10mg has led to an increase of 18% in Atorvastatin concentration without clinical significance.

Niacin: The risk of muscle effects can still be increased when used simultaneously pastetra with niacin.

Colchicin: Cases of muscle disease including muscle pepper have been reported when using atorvastatin simultaneously with colchicin and need to be careful to indicate pastetra with colchicin

The cavalry of the drug:

Due to the absence of studies on the correlation of the drug, not mixing this drug with other drugs.