Atorpa-E 40/10 apimed prevention of cardiovascular disease and hypercholesterol (3 blisters x 10 tablets)

Dosage form Box of 3 blisters x 10 tablets
Specifications Ezetimibe, Atorvastatin
Ingredient Apimed

Ingredient

Composition informationContent
Ezetimibe10mg
Atorvastatin40mg

Uses

indications

Atorpa-E drugs are indicated in the following cases:

Cardiovascular Prevention:

Atorpa-E is indicated to reduce the risk of cardiovascular events in patients with coronary artery disease (CHD) and a history of acute coronary syndrome (ACS), or before or not treated with statin.

Hyper cholesterol:

Atorpa-E is indicated as a supportive therapy for adult patients with primary blood cholesterol (heterozygous heterosexuality with family and non-family nature) or mixed blood lipid disorders when using suitable combined products for:

Patients do not respond to treatment with solitary statin.

Patients were treated with Statin and Ezetimibe.

Hyperlested blood cholesterol (HOFH):

Atorpa-E is indicated as a supportive therapy for a diet in HOFH patients. Patients may also use additional treatments (for example: LDL filter).

Pharmacology

Pharmacological group: Blood lipid disorders

mā ATC: cioba05

Plasma cholesterol is made up of intestinal absorption and endogenous synthesis. Atorpa-E contains Ezetimibe and Atorvastatin, two components that reduce lipid with additional mechanism of action.

Atorpa-E reduces total cholesterol, LDL-Cholesterol (LDL-C), Apolipoprotein B (APO B), Triglycerides (TG) and Cholesterol Lipoprotein are low density (no HDL-C) and increase HDL-C through double inhibition of cholesterol absorption and synthesis.

ezetimibe

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 a molecule of sterol transportation, niiemann-pick cl-like 1 (NPCILI), 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 triglyceride absorption, fatty acids, bile acid, progesterone, ethinyl estradiol, or vitamins A and D in fat.

atorvastatin

Atorvastatin is a selective and HMG-CoA Reductase inhibitor, the speed limit enzyme plays a role in transforming 3-hydroxy-3-methylglutarianl-coenzyme A into Mevabonate, a precursor of sterols including cholesterol. Triglycerides and cholesterol in the liver are combined with very low density lipoprotein (VLDL) and are released into plasma to distribute to peripheral tissues.

Lipoprotein is low density (LDL) created from VLDL and is catabolized mainly through high -sized receptors for LDL (LDL receptor).

Atorvastatin reduces cholesterol and lipoprotein levels by inhibiting HMG-Coa Reductasc and then a cholesterol biosynthesis process in the liver and increases the number of LDL receptors in the liver on the cell surface, enhances the absorption and catabolism of LDL.

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

Atorvastatin is effective in reducing LDL-C in patients with hypertonic blood cholesterol-type blood cholesterol, patients who do not respond to lipid medications.

The drug also works for patients with hyperlested hypertension, heterozygous, hypercholesteroline hypercholesterol, and mixed hyperlipidemia, including diabetes without insulin.

Dynamic pharmacokinetics

absorption

ezetimibe

After drinking, Ezetimibe is absorbed quickly and strongly into a substance that has the effect of Phenolic Glucoronid (Ezetimibe - Glucoronid). Maximum maximum plasma concentration (CMAX) appears about 1 to 2 hours for Ezetimibe-Glucoronid and 4 to 12 hours for Ezetimibe.

Not determined to be absolutely used by Ezetimibe 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 oral bioavailability of Czetimibe when using Czetimibe 10 mg.

Atorvastatin

Atorvastatin is absorbed quickly after drinking. The peak concentration in plasma (CMAX) is achieved 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. The absolute bioavailability of Atorvastatin reaches approximately 12% and the system of systemic use of HMG-CoA Reductase inhibitors reach approximately 30%. Low -body bioavailability is due to clearance before absorbing the whole body in the gastrointestinal mucosa and/ or the initial metabolism in the liver.

distribution

ezetimibe

Ezetimibe and Ezetimibe - Glucoronid linked to plasma proteins, respectively 99.7% and 88 - 92%.

Atorvastatin

Average distribution volume of Atorvastatin reaches approximately 381 liters with> 98% Atorvastatin associated with plasma proteins.

transformation

ezetimibe

Ezetimibe is basically metabolized in the small intestine and the liver thanks to the conjugate with glucoronid (phase II reaction) and then excreted through bile.

have seen minimum oxidation metabolism (stage 1 reaction) in all species of research.

Ezetimibe and Ezetimibe - Glucoronid 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 - Glucoronid are eliminated from plasma slowly with significant reuse in the gut. Half of the excretion of Czetimibe and Ezetimibe - Glucoronid about 22 hours.

Atorvastatin

Atorvastatin is converted by Cytochrom P450 3A4 into Ortho and ParahydroxyLatization derivatives and different beta-oxidation products. These products are also continued to be transformed through glucuronide.

In in vitro, the HMG-CAA Reductase inhibitors of the metabolites of ortho and parahydroxylate chemicals are equivalent to Atorvastatin. About 70% of HMG-CoA Reductase inhibitors are of active metabolites.

Elimination

ezetimibe

In humans, after taking "C-Ezetimibe (20 mg), the total czetimibe accounts for about 93% of the total active active active ingredient in plasma. It has been found to be 78% and 11% of the active active ingredient in the stool and urine obtained for 10 days.

Atorvastatin

Atorvastatin is excreted mainly through bile after the metabolism in the liver and/ or outside the liver. However, Atorvastatin does not significantly participate in the intestinal circulation. The average disposal time of Atorva 1 in plasma is approximately 14 hours. The waste time for HMG-CoA Reductase inhibitors is about 20 to 30 hours due to the participation of active metabolites.

Special subjects

Children

ezetimibe:

  • The absorption and metabolism of Ezetimibe is similar between children and adolescents (10 to 18 years old) and adults. Based on the dose of Ezetimibe, there is no difference in pharmacokinetics between teenagers and adults. There is no dynamic data in children under 10 years old.
  • Atorvastatin's apparent oral clearance in children is similar to adults when compared to body weight.

    ezetimibe:

  • The plasma concentration of total Ezetimibe in the elderly (265 years old) is about 2 times higher than the young (18 to 45 years old).
  • Atorvastatin concentration and more active plasma metabolites in the elderly are healthy than young people while the effects on lipid are similar to young patients.

    ezetimibe:

  • After a single dose of 10 mg Ezetimibe, the average EZETIMIBE curve (AUC) of the total increase is about 1.7 times in patients with mild liver failure (Child-Pugh 5 or 6) compared to healthy people. The total amount of ezetimibe increases about 4 times on day 1 and 14 compared to healthy people. Czetimibe should not be used for patients with severe to severe liver impairment (Child-Pugh> 9), due to the unknown effect of increased body levels of ezetimibe in these patients.
  • Atorvastatin plasma concentrations and metabolites have significant activity (CMAX increases approximately 16 times and AUC increases approximately 11 times) in patients with chronic liver disease due to alcohol (Child-Pough group B).

    ezetimibe:

  • After a single dose of 10 mg Ezetimibe in patients with severe liver failure (n = 8; average CrCl ≤ 30ml/minute 1.73 m), the average AUC of the total ezetimibe increases about 1.5 times compared to the healthy

  • Atorvastatin:

  • Renal failure does not affect plasma concentrations or impact on atorvastatin lipids and active metabolites.

    ezetimibe:

  • The plasma concentration of total ezetimibe in women is slightly higher ( Atorvastatin concentration and active metabolites in women are different from men (women: CMAX is approximately 20% higher and AUC is approximately 10%). Sloc1b1

    atorvastatin:

  • The absorption in the liver of all HMG-CoA Reductase inhibitors including Atorvastatin is related to Oatpib1 transportation. (SLCO1B1 4.521cc) is related to Atorvastatin (AUC) exposure level 2.4 times higher than in objects without this sea genotype (C.521TT). The result of this influence is not known.

    • Before taking Atorpa-E 40/10 apimed prevention of cardiovascular disease and hypercholesterol (3 blisters x 10 tablets)

    How to use

    Atorpa-E medicine is used orally. Take a single dose of the day, during or after meals.

    Dosage

    Atorpa-E drug dose for hypercholesterol and/or coronary artery patients (with a history of acute coronary syndrome):

  • Patients should have an appropriate lipid diet and should continue this diet during treatment with Atorpa-E. Not all doses are available. The usual dose is 10/10 mg/ time/ day. As respected with lipid lowering therapy in use. When the dose is needed, the distance is needed for at least 4 weeks.
  • The recommended dose for patients with hyperlested blood cholesterol family is Atorpa-E 10/10 mg/ day or 80/10 mg/ day. Atorpa-E should use complementary treatments for other lipid reduction treatments (such as LDL removal) in these patients or if these treatments are not available.
  • Should use Atorpa-E before 22 hours or after 24 hours after using bile acid absorption.

    Elderly: No dose adjustment in elderly patients.

    Children: The safety and effectiveness of Atorpa-E in children has not been proven.

    Hepatic failure: Be careful when using Atorpa-E in patients with liver failure. Atorpa-E contraindicent in patients with liver disease.

    Kidney failure: There is no need to adjust the dose in patients with renal failure.

    What to do when overdose?

    ezetimibe

    In clinical studies, Ezetimibe dose of 50 mg/ day for up to 14 days in 15 healthy subjects or a dose of 40 mg/ day for 56 days in 18 patients with primary blood cholesterol, in general, well -tolerated. Only a few reports on the case of overdose and large feces are not accompanied by adverse effects.

    The adverse effects reported when using overdose are not serious. In animals, do not observe toxicity after taking the only dose of 5000 mg/ kg in mice and 3000 mg/ kg in dogs.

    Atorvastatin

    Because Atorvastatin is strongly connected to plasma proteins, the hemorrhage is difficult to significantly increase the clearance of Atorvastatin.

    What to do when you forget a dose? However, if near the next dose time, skip the forgotten dose. Do not take double the dose to compensate for the forgotten dose.

    There is no special requirement on drug treatment after use.

    • Side Effects

    The frequency classification groups are conventional as follows: Very common (> 1/10), common (1/100 to 1/1,000 to 1/10,000 to

    The system unwanted effects frequency rare The rare face Above, lower abdominal pain, constipation, indigestion, flatulence, frequent outside, gastritis, nausea, discomfort in the stomach. Mechanical Common affects the results of testing increases ALT and/or Asat, increases alkaline phosphate, increases blood phosphokinase (CPK), increases gamma-glutamytransferase, increases liver enzymes, abnormal liver function, weight gain. Learning:

    In control clinical research, the serum transaminase level increases significantly (ALT and/ or ASAT23 x ULN, consecutive) is 0.6% in patients treated with Atorpa-E. This increase is often asymptomatic and non-cholecular stasis, self-values ​​return to normal or after treatment.

    Unwanted effects are reported after Atorvastatin/ Ezetimibe or Atorvastatin, Ezetimibe is circulated to the market:

  • Infections and infections: Nasomitis
  • Blood disorders and lymphatic systems: Plateletal reduction
  • immune system disorders: Hypersensitivity, including anaphylaxis, angioedema, rash and urticaria
  • Metabolic and nutrient disorders: Reduction of appetite, anorexia, hyperglycemia, hypoglycemia. Nervous system: Reducing emotions, memory loss, peripheral neuropathy. Stomach, belching, vomiting, dry mouth
  • liver disorders. Hepatitis, gallstones, cholecystitis, cholecyst, fatal and non -fatal liver. muscle. Liver disease, complications due to tendon rupture
  • The following unwanted effects are reported to some statins:
  • Sexual dysfunction. Can go away on its own. Need to carefully monitor unwanted effects and symptomatic treatment. Must stop the medicine and notify the doctor or go to the hospital immediately when there is an unwanted effect.

    • Warnings

    contraindicated

    ATORPA-E medicine contraindicated in the following cases:

  • Hypersensitivity to Atorvastatin, Ezetimibe or any excipients of the drug.

    Caution when using

    muscle disease/muscle pilot

    There have been reports on cases of muscle pattern when using Ezetimibe. Most patients with muscle pattern when used in combination with ezetimibe with a statin. However, there are very rare cases of muscle targets that are still reported when using alone ezetimibe or when ezetimibe combined with other drugs involved in the ability to increase the risk of muscle pattern.

    Atorvastatin as well as other HMG-Coa Reductase inhibitors, in rare cases that can affect skeletal muscle and muscle pain, muscle inflammation and muscle disease can progress into muscle syndrome, a situation that can be life-threatening manifested by creatin phosphokinase levels (CPK) significantly increased (> 10 times the upper limit of the normal level) Myoglobinuria can lead to renal failure.

    Before treatment

    Atorpa-E needs to be used cautiously in patients with factors affecting muscle syndrome. CPK tests should be done before starting treatment in the following cases:

  • Hypertman
    • impaired renal function
  • History of itself or family history of genetic muscle disease
  • History of muscle disease due to statin or fibrat previous
  • History of liver disease and/or drinking lots of alcohol
  • older patients (70 years old).

    Creatin phosphokinase test (CPK)

    Do not measure the concentration of creatin phosphokinase (CPK) after exertion exercise or when there is the presence of a certain cause that can increase the CPK concentration because this can make the result deviation
    results. If the concentration of CK increases significantly before treatment (> 5 times the upper limit of normal level), a test should be done to redefine within 5-7 days.

    during treatment

    Ask the patient to notify immediately when muscle pain, muscle weakness or muscle spasticity especially when accompanied by fatigue or fever, or if the signs and symptoms still exist after stopping treatment with Atorpa-E.

    If these symptoms occur while patients use Atorvastatin, CPK concentration should be measured.

    If the CPK concentration increases significantly (> 5 times the upper limit of normal level) should stop treatment.

    If muscle symptoms are serious and cause daily discomfort, even if the CPK concentration

    If the symptoms are relieved and the CPK concentration returns to normal, it is advisable to consider using Atorpa-E or another statin at the lowest dose and closely monitoring.

    It is necessary to stop using Atorvastatin if the CK concentration increases significantly in terms of clinical (> 10 times the upper limit of normal level), or if diagnosed or suspected of muscle pilot.

    There have been very rare reports on muscle necrotic disease due to immunity (IMNM) during or after treatment with some statins. The clinically IMNM shows continuous muscle aches and increases serum creatinin. These manifestations continue to stop treating with statin.

    Because Atorpa-E contains Atorvastatin, the risk of muscle and muscle elimination increases when Atorpa-E is simultaneously used with drugs that can increase the level of Atorvastatin in plasma such as strong inhibitors or CYP3A4 or shipping proteins (e.g. Colchicin, Ciclosporin, Telithromycin, Clarithromycin, Delavidin, StirPentol, StirPentol, StirPentol, StirPentol, StirPentol, StirPentol, StirPentol Ketoconazole, Voriconazole, Itraconazole, Posaconazole and HIV Protease inhibitors include Ritonavir, Lopinavir, Atazanavir, Indinavir, Darunavir ...).

    The risk of muscle disease can also increase when coordinated with gemfibrozil and other fibrats, erythromycin, niacin, antiviral antiviral drugs, Boceprevir, Telaprevir, ElbasVL, Grazeprevir, or combined Tipranaviri Ritonavir.

    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).

    Do not use Atorpa-E simultaneously with fusidic acid. In patients needed to use fusidic acid, statin should be stopped during fusidic acid treatment.

    There have been reports on cases of muscle pattern (some deaths) in patients who are using fusidic acid in combination with statin (see interaction).

    Statin therapy can be reused after 7 days from the last dose of fusidic acid.

    In special cases, if it is required for prolonged treatment with fusidic acid, for example, to treat severe infections, the simultaneous use of Atorpa-E with fusidic acid should be considered on the basis of specific cases under strict medical monitoring.

    Liver enzymes:

    In control clinical trials that combine Atorvastatin and Ezetimibe, the continuous transaminase increased (> 3 times limited to normal levels) (see unwanted effects).

    Check the liver function before starting to use Atorpa-E and often afterwards. Liver function should be monitored in patients with signs or symptoms of liver damage. Patients with high transaminase levels should be monitored until the abnormalities have been resolved.

    If the transaminase concentration is still higher than 3 and the upper limits of normal levels, the dose or stop use of Atorpa-E (see the unwanted effect).

    Be cautious when using Atorpa-E for patients to drink a lot of alcohol and/ or a history of liver disease.

    Hepatic failure:

    Due to the unknown effect of increasing Ezetimibe concentration in patients with medium or severe liver failure, Atorpa-E should not be used for patients bouncing (see pharmacokinetics).

    Fibrats:

    Not studying safety and efficiency of using Ezetimibe combination with fibrats. Therefore, should not use Atorpa-E combined with fibrats.

    ciclosporin:

    Be careful when starting with Atorpa-E during treatment with ciclosporin.

    Need to monitor ciclosporin levels in patients using Atorpa-E combined with ciclosporin.

    anticoagulants:

    Should follow the appropriate internationalization of internationalization (INR) when combining Atorpa-E with wafarin, anti-anticoagulant drug resistant to vitamin K or Fluindion.

    Stroke prevention by actively reducing cholesterol levels (Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SparCl)):

    According to an analysis of posting analysis of stroke groups in patients with no new coronary artery disease or transient infarction, the rate of hemorrhagic stroke in patients begins to treat atorvastatin 80 mg higher than the same fake. Increased risk has been especially noted in patients who have had a stroke or a disabled infarction before treatment.

    For patients who have had a hemorrhagic stroke or an infarction, the balance between the risk and benefits of Atorvastatin 80 mg has not been determined and the potential risk of hemorrhage stroke should be carefully considered before starting treatment (see pharmacokinetics).

    Interstitial lung disease:

    Some special cases of interstitial lung disease have been recorded when using some statins, especially long -term treatment (see unwanted effect). The most common manifestation includes shortness of breath, dry cough and impaired health in general 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 are at risk of hyperglycemia (blood sugar at 5.6 to 6.9 mmol, body mass index (BMI)> 30 kg/m, increase triglycerides, hypertension) should be monitored both clinical and biochemical according to national instructions.

    excipients:

    The drug contains lactose. Patients with rare genetic diseases are galactose, deficiency of lactase enzyme or malposive glucose-galactose should not be taken.

    Using drugs for pregnant and lactating women

    Pregnant women:

    Atherosclerosis is a chronic process, and shyly treating conventional lipid medications during pregnancy has little impact on the risk of long -term associated with hypercolenic cholesterol.

    Contraindicated to use Atorpa-E during pregnancy.

    Simultaneous use of Ezetimibe and Atorvastatin in pregnant mice shows an abnormal increase in bone "reducing bone chemistry in sternum burning" related to high doses of Ezetimiber Atorvastatin. This is related to the fetal weight reduction. In pregnant rabbits, observed a small percentage of skeletal abnormalities.

    Atorvastatin

  • The safety of Atorvastatin when used for pregnant women has not been determined. There have been dangerous reports on birth defects after exposure to HMG-Coa Reductase inhibitors in the uterus.

    ezetimibe:

  • There is no clinical data on the use of ezetimibe in pregnant women.

    • breastfeeding women:

    Due to the potential risk of serious side effects, women treated with Atorpa-E should not breastfeed. Mouse research shows that Ezetimibe is secreted into milk. In mice, agriculture atorvastatin in plasma and its active metabolites are equivalent to the substances found in milk. It is unknown whether the active ingredients of Atorpa-E are excreted in breast milk, so Atorpa-E is contraindicated in nursing women.

    The effect of the drug on driving and operating machinery

    Atorpa-E does not affect or negligible on the ability to drive and operate machinery. However, the possibility of dizziness may be encountered after using Atorpa-E.

    Drug interaction

    Interactive force

    Atorvastatin, a component of Atorpa-E, is metabolized by Cytochrom P450 3A4 (CYP3A4) and is a substance to transport protein for example, transporting absorption in OatPB1 liver.

    The simultaneous use of the drugs are inhibitors of CYP3A4 or transport proteins that can lead to increased cubic atorvastatin levels and increase the risk of muscle disease. The risk can also increase when using Atorpa-E simultaneously with other drugs that are likely to cause muscle disease such as fibrats and ezetimibe.

    Mobile interaction

    Effect of other drugs on Atorpa-E:

    ezetimibe

    Anti -acid drugs: 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.

    Cholestyramin: Concomitance with Cholestyramin reduces the average AUC of total czetimibe (Ezetimibe + Ezetimibe Glucuronid) by 55%. The degree of reduction of LDL-C supplement Atorpa-E to Cholestyramin therapy may be worse due to this interaction.

    ciclosporin:

  • In a study in 8 patients after kidney transplantation with increased creatinine> 50 ml/ min when using the fixed dosage of ciclosporin, the only 10 mg Ezetimibe dose increased by 3.4 times (2.3 to 7.9 times) The average of the total ezetimibe compared to a healthy control group from another study (n = 17). (Creatinin clearance 13.2 ml minute 1.73m) has been used many drugs, including ciclosporin, increasing czetimibe concentration more than 12 times compared to the control group. (from 10% to an increase of 51%) compared to when using only 100 mg of ciclosporin.

    Fibrats: Use in combination with Tenofibrat or Gemfibrozil, increasing the total concentration of Ezetimibe about 1.5 - 1.7 times but not clinical significance. Contraindications to Atorpa-E simultaneously with Gemfibrozil and other fibrats are not recommended.

    Atorvastatin

    CYP3A4 inhibitors:

    The strong CYP3A4 inhibitors have been shown to significantly increase Atorvastatin levels (see Table 1 and the specific information below). Strong CYP3A4 inhibitors should be avoided (for example, ciclosporin, telithromycin, clarithromycin, delavidrin, stiripentol, ketoconazol, voricazol, otraconazol, posaconazole and HIV protease inhibitors such as ritonavir, lowazir, actazanavir, indira, indepir, indirin Darunavir, ...). In cases where it is impossible to avoid the simultaneous use of protease inhibitors with Atorpa-E, it is advisable to use lower doses than the original dose and need to monitor the appropriate forest.

    Medium CYP3A4 inhibitors (such as erythromycin, diltiazem, verapamil and fluconazole) may increase the concentration of Atorvastatin in plasma. The increased risk of muscle disease has been recorded when using erythromycin simultaneously with the 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 used simultaneously with Atorpa-E can cause an increase in contact with Atorvastatin. Therefore, Atorvastatin should be considered at a lower doses and the clinical monitoring is suitable for patients to use Atorvastatin simultaneously with medium -level CYP3A4 inhibitors. Appropriate clinical monitoring after starting or after
    adjust the CYP3A4 inhibitors.

    Anti -cancer protein inhibitors and (BCRP):

    Concomitance BCRP inhibitors (such as Elbasvir and Grazoprevir) may increase the level of lattvastatin in plasma and increase the risk of muscle disease. Therefore, it is necessary to consider adjusting the dose of Atorvastatin. Simultaneous use of Elbasvir with Grazoprevir with Atorvastatin increases the level of Atorvastatin in plasma 1.5 times (see Table 1). Therefore, the atorpa-E dose should not exceed 10/20 mg daily in patients who use drug products and contain elbasvir or grazeprevir.

    Cytochrom P450 344:

    Simultaneous use Atorvastatin with P450 3A4 (such as Efavirenz, Rifampicin, St. John's Wort) may reduce the concentration of Atorvastatin in plasma.

    Due to the dual interaction mechanism of Rifampicin (Cytochrom P450 3A4 touch and OatP1B1 transport inhibitors in the liver), Rifampicin can significantly reduce the level of plasma Atorvastatin levels of rifampicin on Atorvastatin concentration in liver cells, but if it is not known, it cannot be prevented with a combination of treatment.

    Transport protein inhibitors:

    Transport protein inhibitors (eg ciclosporin) may increase the body's body contact level. The influence of the inhibition of the liver absorption substances on the Atorvastatin concentration in liver cells is not known. If these drugs cannot be avoided, they should reduce the dose and clinical monitoring to control the effectiveness of treatment.

    gemfibrozil/ fibrats:

    The use of solitary fibrats is sometimes related to mechanical events, including muscle pattern. The risk of these events can be increased by simultaneous use of fibrats and atorvastatin. If it is not possible to avoid these drugs, the lowest atorvastatin dose should be used to achieve the purpose of treatment and need to monitor the patient appropriately.

    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 appropriately for these patients.

    Colestipol: Atorvastatin concentration in plasma and lower active metabolites (approximately 25%) when concurrent Colestipol together with Atorvastatin. However, the lipid reduction effect is greater when
    is simultaneously used atorvastatin and colestipol compared to when using one of these two drugs alone.

    Fosidic acid: The risk of muscle disease, including muscle pattern increases when using fusidic acid and statin. Cases of muscle pattern (some deaths) have been told
    when using fusidic and statin acid simultaneously. If the body is needed with fusidic acid, should stop treatment with Atorvastatin during fusidic acid treatment.

    Colchicin: Although there has been no study on drug interaction between Atorvastatin and Colchicin, cases of muscle disease have been reported when Atorvastatin is simultaneously used with colchicin, so be careful when indicated atorvastatin general with colchicin.

    boceprevir: Atorvastatin's exposure increases when combined with boceeprevir. If it is necessary to coordinate with Atorpa-E, it is necessary to start with Atorpa-E at the lowest possible dose and then increase the dose under close supervision until the desired clinical effect does not exceed the daily dose of 10 20 mg.

    In patients who are being treated with Atorpa-E, the daily dose of Atorpa-E should not exceed 10/20 mg when used with BoCeprevir.

    Atorvastatin in unknown liver cells. If these drugs cannot be avoided, they should reduce the dose and clinical monitoring to control the effectiveness of treatment.

    gemfibrozil/ fibrats:

    The use of solitary fibrats is sometimes related to mechanical events, including muscle pattern. The risk of these events can be increased by simultaneous use of fibrats and atorvastatin. If it is not possible to avoid these drugs, the lowest atorvastatin dose should be used to achieve the purpose of treatment and need to monitor the patient appropriately.

    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 appropriately for these patients.

    Colestipol:

    Atorvastatin concentration in plasma and lower active metabolites (approximately 25%) when using Colestipol simultaneously with Atorvastatin. However, the lipid reduction effect is greater when using Atorvastatin and Colestipol compared to when using one of these two drugs alone.

    Fosidic acid:

    The risk of muscle disease, including muscle pattern increases when using fusidic and statin acid simultaneously.

    The mechanism of this interaction is not known. Cases of muscle pattern (some deaths) have been told when using fusidic and statin acid simultaneously. If the body is needed with fusidic acid, should stop treatment with Atorvastatin during fusidic acid treatment.

    colchicin:

    Although studies have not been conducted on drug interaction between Atorvastatin and Colchicin, cases of muscle disease have been reported when Atorvastatin is used simultaneously with Colchicin, so be careful when indicating Atorvastatin with Colchicin.

    boceprevir:

    Atorvastatin's

    increases in contact with BoCeprevir. If it is necessary to coordinate with Atorpa-E, should start with Atorpa-E at the lowest possible doses and then increase the dose under close supervision until the desired clinical effect does not exceed the daily dose of 10 20 mg. In patients who are being treated with Atorpa-E, the daily dose of Atorpa-E should not exceed 10/20 mg when used with BoCeprevir.

    The influence of Atorpa-E on the dynamics of other drugs

    ezetimibe:

    In preclinical studies, it has been shown that ezetimibe does not cause enzymes to metabolize Cytochrom P450. There is no clinical pharmacokinetic interaction between Ezetimibe and drugs metabolized by Cytochrom P450 1A2, 2D6, 2C8, 2C9, and 3A4, or N-acetyltransferase.

    Anticoagulant. In a study on 12 healthy male volunteers, simultaneously used with Ezetimibe (10 mg once a day) does not significantly affect the bioavailability of warfarin and prothrombin time.

    However, after the drug circulated on the market, there was a report on Inr increasing in patients using Ezetimibe simultaneously with Warfarin or Fluindion. Therefore, when using Atorpa-E simultaneously with warfarin or other anticoagulants, or fluindion, should monitor the appropriate INR index.

    Atorvastatin

    Digoxin: simultaneously use repeated dosgoxin and Atorvastatin 10 mg increases the equilibrium concentration of digoxin. Patients who are being treated with digoxin should be monitored regularly.

    Oral contraceptive: simultaneous use of Atorvastatin and oral contraceptives increases the plasma concentrations of Norethisteron and Ethinyl Estradio.

    warfarin:

    In a clinical study in patients who are under long -term treatment with warfarin, simultaneously taking Atorvastatin 80 mg daily reduces prothrombin time to 1.7 seconds in the first 4 days, this value is normal for 15 days from the start of Atorvastatin.

    Although there are very rare cases of clinical interactions are reported, prothrombin time should be determined before starting treatment with Atorpa-E in patients who are taking anticoagulant drugs, and we often often start treatment. Apply similarly to the cases of changing the dose or stopping atorpa-e treatment.

    Atorvastatin treatment is not related to bleeding or changing prothrombin time in patients without anticoagulants.

    Table 1: Effect of other drugs on the pharmacokinetics of Atorvastatin.

    Simultaneous and dosage

    Tipranaviri 500mg, 2 times/day or ritonavir 200mg, 2 times/day used for 8 days (14th to 21th day) 40mg on the first day, 10 mg on the 20th day increased x 9.4 if needed in combination with Atorpa-e ciclosporin 5.2mg/ kg/ day, maintenance dose 10 mg/ time/ day for 28 days increased x 8.7 Increase X 5.9 if required to be combined with Atorpa-E should be used with lower maintenance dose. When using the dose greater than 20/10mg, clinical monitoring should be closely monitored. Ritonavir 300mg, 2 times/ day on Thursday to 7, increasing the dose to 400 mg twice a day on the 8th day, Thursday to 18, 30 minutes after using Atorvastatin 40 mg/ day/ day, in 4 days increased x 3.9
    if required to combine with Atorpa-E, should be used in lower maintenance. When using the dose greater than 40/10mg should closely monitor clinically Time/day, in 4 days 40 mg single dose increased x 3.3

    Fosamprenavir 1400 mg 2 times/day, in 14 days 10 mg/time/day, in 4 days increased x 2,3 Increase X 1,7^ Time/day, in 28 days 40 mg of a single dose increased by 51%

    clinical monitoring in patients after starting or adjusting the diltiazem dose There is a special recommendation

    Amlodipine 10 mg single dose 80 mg The only dose increased by 18%

    no recommendation
    Special Week Discount less than 1% ^ No recommendations
    Special Especially

    Efavirenz 600 mg/time/day, in 14 days 10 mg in 3 days 41%off no recommendations
    Special Most increased by 30% If required to use Atorpa-E and Rifampicin at the same time, it should be closely monitored clinically

    gefillozil 600 mg twice a day, in 7 days 40 mg of a single dose increased by 35% Unlike recommended It is not recommended

    boceprevir 800 mg 3 times/day, in 7 days 40 mg single dose increased x 2,3 recommendation of lower starting dose and closely monitoring clinically. Atorpa-E's daily
    daily dose must not exceed 20/10 mg when used in the congestion with BoCeprevir. When used simultaneously
    with drugs that contain elbasvir or grazoprevir. If you drink a 240 ml grapefruit juice, it will lead to 20.4% AUC of activated orthhydroxyl metabolites. Significant amount of grapefruit juice (more than 1.2 liters daily in 5 days increases AUC of Atorvastatin 2.5 times and AUC of active ingredients (Atorvastatin and metabolites).

    Table 2: The influence of Atorvastatin on the dynamics of the medications simultaneously.

    simultaneously used Time/day for 10 days Digoxin 0.25 mg/time, in 20 days increased by 15% patients undergoing with digoxin should be followed appropriately Mg
  • ethinylelestradiol 35 mg
  • With Norethisterone increased by 28%
  • with EthinyleLestradiol increased by 19%
    • There is no special recommendation 1400 mg 2 times/day, in 14 days discount 27% no special recommendations

    Storage

    Leave a cool place, avoid light, temperature below 30⁰C.

    Other drugs

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