Ezenstatin 10/20 Agimexpharm backup cardiac incident (4 blisters x 7 tablets)

Code ATC: C10BA05.

Plasma cholesterol has two origin: exogenous origin (absorbed from the intestine) and endogenous origin (self -synthetic body). Ezenstatin is a combination of two substances Ezetimib and Atorvastatin, which reduces plasma cholesterol with both ways to inhibit the absorption and cholesterol synthesis.

ezetimib:

Ezetimib reduces blood cholesterol by inhibiting the absorption of cholesterol in the small intestine.

Ezetimib localized at the brush edge of the small intestine and inhibit cholesterol absorption, leading to a decrease in cholesterol transportation from the intestine into the liver. This helps reduce cholesterol storage in the liver and increases the clearance of cholesterol from the blood; This separate mechanism adds the effects of statins.

atorvastatin:

Atorvastatin is a competitive inhibitor with hydroxymethylglutaryl Coenzym (HMG - CoA) Reductase, preventing HMG - CoA into Mevalonate, precursor of cholesterol, thus inhibiting cholesterol biosynthesis, reducing cholesterol in liver cells, stimulating LDL receptor synthesis (low -weight lipoprotein billion) LDL transferred from blood, resulting in a decrease in plasma cholesterol levels. At normal doses, HMG - CoA Reductase is not completely inhibited, so there is still enough meevalonic acid for many metabolic processes.

All statins reduce LDL levels very effectively, in which Atorvastatin reduces the strongest LDL cholesterol (25 - 61%) compared to any drug used alone, and is prospective for patients who need to reduce cholesterol, which is now only achieved when combined with drugs.

Atorvastatin increases the concentration of HDL cholesterol (high density lipoprotein) from 5 - 15% and thus lowering LDL/HDL ratios and total/HDL cholesterol.

Atorvastatin also reduces plasma triglycerides at a lower level (10 - 30%) by increasing the clearance of VLDL (Lipoprotein very low density) residues thanks to the LDL receptor.

Response treatment with Atorvastatin can be seen within 1-2 weeks after starting the drug and usually reaches up to 4-6 weeks.

Maintain maintenance during long -term treatment. In clinical studies, evidence suggests that Atorvastatin significantly reduces coronary artery events, all cardiovascular events have existed and reduces the total number of deaths in people with coronary artery disease (with a history of angina or acute myocardial infarction) and people with plasma cholesterol 5.5 mmol/liter or higher.

Atorvastatin also plays a role in the prevention of primary (level 1) coronary artery disease in patients with cholesterol hyperplasia that is at high risk of coronary artery event.

Dynamic pharmacokinetics

absorption

ezetimib:

After drinking, Ezetimib is quickly absorbed and combined into the Ezetimib-glucuronid form. The maximum concentration in plasma (CMAX) reaches about 1-2 hours after drinking for ezetimib-glucuronid and about 4-12 hours after drinking for ezetimib. Food (fat or non -fat) does not affect the bioavailability of ezetimib.

atorvastatin:

Atorvastatin is quickly absorbed after drinking and is not affected by food. Peak concentration in plasma is achieved in 1-2 hours. The absolute bioavailability of Atorvastatin is about 14%.

distribution

ezetimib:

Ezetimib and Ezetimib - Glucuronid associated with plasma proteins at 99.7% and 88 - 92%.

atorvastatin:

Over 98% Atorvastatin is connected to plasma proteins.

transformation

ezetimib:

Ezetimib is metabolized mainly in the small intestine and liver through a combination of glucuronid. Both Ezetimib and Ezetimib-Glucuronid are slowly eliminated from plasma due to the intestinal cycle. The half-life of Ezetimib and Ezetimib-Glucuronid is about 22 hours.

atorvastatin:

Atorvastatin is mainly metabolized in the liver (> 70%) by the microsom cytochrom P450 (CYP) enzyme system, mainly due to isoenzyme 3A4 (CYP 3A4) into substances with or non -active metabolites.

Elimination

ezetimib:

After taking 14 C-Ezetimib (20 mg), about 93% Ezetimib is present in plasma. About 78% excreted through feces and 11% excreted through urine within 10 days. After 48 hours, there is no drug present in plasma.

atorvastatin:

Atorvastatin eliminates many feces, excreted through the kidney

Be cautious when using

It is necessary to consider when taking this drug (because the drug contains a statin group) for patients with risk factors leading to muscle damage. The drug in the statin group is at risk of causing harmful reactions to the muscle system such as muscle atrophy, muscle inflammation, especially for patients with risk factors such as patients over 65 years old, patients with untreated thyroid diseases, patients with kidney disease. Need to closely monitor the harmful reactions during drug use.

Before starting treatment, it is necessary to eliminate the causes of hypercholesterol blood cholesterol such as: under -control diabetes, thyroid disobsius, kidney syndrome, blood protein disorders, biliary liver disease, due to some other drugs, alcohol addiction and total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides.

Must conduct periodic lipid quantification, with a distance of less than 4 weeks, and adjust the dosage according to the patient's response to the drug.

The goal of treatment is to reduce LDL cholesterol. Therefore, it is necessary to use LDL cholesterol levels to start treatment and evaluate treatment. Only when the LDL cholesterol is not tested, will the total cholesterol use to monitor treatment.

Try to control blood cholesterol with appropriate diet, exercise, lose weight in obese patients and treat other basic diseases.

Need to do liver enzyme test before starting statin treatment and in case of clinical indications for testing later.

Consider monitoring Creatin Kinase (CK) in the case:

Before treatment, CK tests should be conducted in the following cases: impaired renal function, hypothyroidism, self -history or family history of genetic muscle disease, a history of muscle disease due to the use of statin or fibrat before, a history of liver disease and/or drinking lots of alcohol. Elderly patients (> 70 years old) have risk factors for muscle panoda, the possibility of drug interactions and some special patients.

In these cases, the benefits/risks should be considered and monitor patients clinically when treated with insulin. If the results of CK test> 5 times the upper limit of normal levels, do not start treatment with statin.

During statin treatment, patients need to notify when there are muscle manifestations such as muscle pain, muscle stiffness, muscle weakness ... When there are these manifestations, patients need to do CK test to take appropriate interventions.

Only use this medication for women of reproductive age when they are certainly not pregnant and only in the case of hyperlesterol very high without responding to other drugs.

This drug contains lactose. Patients with rare genetic problems in tolerance Galactose, Lapp Lapp Lactase or Glucose-Galactose should not take this drug.

The effect of the drug on driving and operating machinery

There is no evidence of the effect of the drug on the ability to drive, operate machinery. However, it should be noted that side effects such as headache, dizziness, blurred vision may occur during the medication period.

Use drugs for women during pregnancy and lactation

Pregnancy

Contraindicated to use this drug for pregnant women. There is no clinical data on the use of Ezetimib and Atorvastatin during pregnancy.

Women who are likely to be pregnant or are using contraception should consult a doctor carefully before treatment with this drug. Do not use this medication if suspected of pregnancy.

There is no information on the toxicity of the fetus.

Breastfeeding period

Do not know whether the drug is excreted in breast milk or not so contraindicated use of this medication in breastfeeding women.

Drug interaction

The risk of muscle disease during long -term treatment with this drug is increased (due to containing ezetimib and atorvastatin) when taken simultaneously with the derivatives of fibric acid, niacin, cyclosporin, or powerful CYP3A4 inhibitors (for example Clarithromycin, HIV -HIV -and HIV -HIV -HIV -HIV -HIV -/HIV -HIVN -HIVN -HIV and ITRASONAL).

Cytochrom CYP3 A4 inhibitors: Avoid treating this combination of drugs with cyclosporin, erythromycin, gemfibrozil, otraconazole, ketoconazole (due to Cytochrom CYP3 A4), with Niacin at the dose of lipid (> 1g/day), with Colchicin and with other fibrat medications for fibrat blood groups Causing muscle and muscular inflammation.

Coumarin derivatives: Atorvastatin can increase the effect of warfarin. Prothrombin must be determined before starting this medication and regular monitoring in the early stages of treatment to ensure no change in prothrombin time.

Bile acid -mounted plastic: Atorvastatin and bile acid -mounted plastic (Cholestyramin, Colestipol) have a supplementary mechanism for each other; Combining these groups of drugs has a plus effect on LDL cholesterol. However, this group of drugs can significantly reduce the bioavailability of Atorvastatin when taken with them, so the time to use these two drugs must be about 2 hours apart to avoid clear interaction due to the drug attached to the plastic.

Other lipid medications: limit this combination of drugs with other lipid medications because of the ability to increase the risk of muscle disease.

Although there is no clinical interaction studies in clinical interaction, there is no clinical significant interaction with Atorvastatin with enamel inhibitors, angiotensin, beta blockers, calcium channel blockers, diuretics and nonsteroidal anti -inflammatory drugs.

Rifampin: Rifampin reduces Atorvastatin concentration when combined with 2 drugs, those drugs must be taken at the same time, because taking atorvastatin after drinking rifampin reduces plasma Atorvastatin levels.

diltiazem: Increases the concentration of Atorvastatin in plasma, at risk of muscle fiber, kidney failure.

Oral contraceptive pills: Concomitance with oral contraceptives containing norethindron and ethinyl estradiol increases the value of the area under the concentration - time (AUC) curve (AUC) of Norethindron and Ethinyl Estradiol is about 30% and 20%. This increase should be considered when choosing oral contraceptives for women to use Atorvastatin.

antacids: Use Atorvastatin simultaneously with antacids containing magnesi and aluminum hydroxyd, plasma concentration of Atorvastatin is reduced by about 35%. When taking the same antacids of Ezetimib's absorption, it does not affect the bioavailability of Ezetimib. The reduction of this absorption rate is considered without clinical significance.

Protease inhibitors of HIV and hepatitis C (HCV): The simultaneous use of Atorvastatin with protease inhibitors of HIV and hepatitis C (HCV) can increase the risk of the most serious muscle damage, which is pattern, kidney damage leading to kidney failure and can be fatal, so it is necessary to reduce the dose of Atorvastatin as recommended in the following table: