Inedji

Inegy is a lipid-lowering medication.

Indications Inedji

It is used to treat hypercholesterolemia.

The primary form of the disease.

As an excipient in combination with a diet in people with the primary form of hypercholesterolemia (hereditary or non-familial heterozygous nature) or hyperlipidemia of a mixed nature, when you need to use a complex medication. Assign persons who have not achieved the desired effect when using only statins, and in addition to people who previously used ezetimib and statins.

To reduce the frequency of complications associated with the work of the CAS in people with coronary artery disease and an increased likelihood of such effects.

Hereditary hypercholesterolemia homozygous nature.

As an auxiliary component with diet. In addition, there may be additional therapy (for example, LDL-apheresis).

Release form

The release of the drug is made in pill form, 14 pieces inside the cell plate. In a pack - 2 records.

Pharmacodynamics

Inegy is a lipid-lowering substance that inhibits intestinal absorption of cholesterol with its sister plant sterols, and also endogenous cholesterol binding processes.

The drug contains simvastatin with ezetimibe (these are lipid-lowering elements with the complementary principle of therapeutic effect). The drug lowers the increased levels of cholesterol cholesterol, LDL cholesterol, and besides this apo-B, triglycerides and cholesterol-XLPL. At the same time, it increases the HDL cholesterol values, providing a double effect - suppression of cholesterol absorption and binding.

Ezizib

Component inhibits intestinal absorption of cholesterol. The mechanism of its medicinal effect differs from other groups of drugs that reduce cholesterol levels (for example, fibrates with statins, resins, and also plant stanols). The molecular effect of ezetimiba is directed to the NPC1L1 sterol transporter, whose function is the intestinal absorption of phytosterols with cholesterol.

The element is located in the area of the brush strips of the small intestine and inhibits the absorption of cholesterol, reducing the volume of intestinal cholesterol delivered inside the liver. Statins reduce hepatic cholesterol binding. Both of these mechanisms contribute to an additional decrease in cholesterol levels. Ezetimibe has no effect on the absorption of bile and fatty acids, triglycerides with ethinyl estradiol and progesterone or fat-soluble calciferol with retinol.

Simvastatin.

After oral administration, simvastatin, which is an inactive lactone, undergoes a process of hepatic hydrolysis followed by the formation of an active β-hydroxy acid form (it has a powerful inhibitory effect on the activity of HMG-CoA reductase). This enzyme acts as a catalyst for the earliest and most important phase of cholesterol biosynthesis - the process of transformation of HMG-CoA into a mevalonate component.

The element lowers both increased and standard LDL cholesterol levels. LDL substances are formed from VLDL and for the most part are subject to catabolism with the participation of high-affinity LDL-terminations. Along with a decrease in the level of LDL, simvastatin can decrease the VLDL cholesterol values, and in addition induce the activity of LDL endings, which reduces the production and increases the catabolism of LDL cholesterol.

Simvastatin therapy significantly reduces the values of apo-B. At the same time, the component moderately increases HDL cholesterol levels and plasma TG level. All these changes lead to a decrease in the proportions of total cholesterol / HDL, as well as LDL / HDL.

Pharmacokinetics

Suction.

Ezizib

When used orally, the component is absorbed at a high rate and conjugated to form a therapeutically active phenolic glucuronide (ezetimib glucuronide). Plasma Cmax is noted after 1-2 hours (ezetimib-glucuronide) and 4-12 hours (ezetimib).

Eating (with high or low fat) does not affect the severity of bioavailability of the substance.

Simvastatin.

After administration of simvastatin, the level of active β-hydroxy acid within the circulatory system is less than 5% of the portion used (after the 1st hepatic passage). In addition to β-hydroxy acid, 4 more active metabolic products are excreted inside human plasma. If the substance is consumed before meals (on an empty stomach), the plasma values of the total and active inhibitors remain the same.

Distribution processes.

Ezizib

The active element with ezetimib glucuronide undergoes plasma protein synthesis, respectively, at 99.7%, and also 88-92%.

Simvastatin.

The intraplasma protein synthesis of simvastatin with β-hydroxy acid is 95%. Pharmacokinetic tests demonstrated that simvastatin does not undergo tissue cumulation. The values of Сmax inhibitors are recorded after 1.3-2.4 hours after the introduction of the drug.

Exchange processes.

Ezizib

The initial metabolic processes of ezetimiba develop inside the liver and small intestine through conjugation with glucuronide (the reaction occurs at the 2nd stage), and then it is excreted with bile. Minimal oxidative exchange processes (occurring at the first stage of the reaction) are observed in all phases of the transformation of the substance.

Ezetimibe along with ezetimib glucuronide are the main components that are observed inside the blood plasma. They constitute about 10-20%, as well as 80-90% of the total plasma indicators of drugs. These elements at low speed are excreted from the blood plasma when recirculation occurs inside the liver with intestines.

The half-life of components is approximately 22 hours.

Simvastatin.

Simvastatin is a non-active lactone that undergoes rapid hydrolysis in vivo, which converts it into β-hydroxy acid. Hydrolysis processes mainly take place inside the liver, and its plasma velocity is extremely low.

The substance is well absorbed and participates in active extraction during the 1st intrahepatic passage. Hepatic extraction is determined by the speed of blood circulation inside the liver.

Drug effects of drugs initially directed to the liver, after which the metabolic products are excreted in the bile. In the systemic circulation, active degradation products penetrate poorly.

The half-life of β-hydroxy acid after i / v injection is 1.9 hours.

Excretion.

Ezizib

In 14 C-ezetimibe (20 mg), taken orally, volunteers inside the blood plasma determined 93% of total ezetimibe (based on total plasma radioactivity). About 78%, as well as 11% of the used radioactive dose, is excreted with feces and urine for 10 days. After 48 hours, there were no radioactive indicators inside the blood plasma.

Simvastatin.

Simvastatinic acid is transported with hepatocytes with the participation of the OATP1B1 transporter.

Simvastatin is a substrate of the efflux transporter of the breast cancer resistance protein (BCRP).

For 96 hours after oral administration of radioactive simvastatin, it was excreted in the urine (13%) and feces (60%). The amount of medication excreted in the feces includes absorbed medication, derived from the bile, as well as unabsorbed.

After applying the β-hydroxy acid metabolic product, only 0.3% of the used portion was excreted in the urine in the form of inhibitor substances.

Dosing and administration

The primary form of hypercholesterolemia.

Before the treatment cycle begins, the patient must be transferred to a standard diet, which reduces the cholesterol index, which he needs to observe the entire period of therapy.

Portion of Ineji is determined personally, taking into account the initial values of LDL cholesterol, the goal of therapy and the clinical response to its implementation. The medication is consumed once a day, in the evening, without reference to the reception of food.

The range of dosage portions is 10 / 10-10 / 40 mg per day. Basically, first take the drug in a dosage of 10/20 or 10/40 mg per day.

During the selection of the portion or since the start of therapy, blood lipid indicators should be monitored (with a minimum of 4 weeks intervals) and the size of the dosage should be changed if necessary.

Hereditary hypercholesterolemia homozygous nature.

First you need to take the medicine in a portion of 10/40 mg per day (evening reception). The drug is used as an auxiliary therapeutic element with a different cholesterol-lowering treatment (for example, LDL-apheresis) or if such therapy is not available.

Use with other medicines.

Inegy should be administered at least 2 hours before or maximum after 4 hours after the use of sequestrants associated with bile acids.

Persons who take amlodipine, diltiazem, amiodarone with verapamil or niacin in lipid-lowering doses should be administered no more than 10/20 mg of the drug per day.

Children.

The initial stage of therapy should be carried out under the supervision of a medical professional.

For children 10-17 years of age, information on the use of drugs is limited (pubertal period: boys - 2nd or higher stage of the Tanner scale; girls - at least 1 year after the appearance of menarche). First you need to take the drug in portions of 10/10 mg, 1-fold per day. The recommended dosage range is 10 / 10-10 / 40 mg medication per day.

Persons with liver failure.

It is impossible to prescribe a drug to people with moderate (7-9 points in the Child-Pugh classification) or severe (more than 9 points) violation.

People with problems with kidney function.

People with chronic renal failure and GFR <60 ml / min / 1.73 m ^{2 are} required to take 10/20 mg of the drug once a day in the evenings. Larger portions are used with extreme care.

[2]

Use Inedji during pregnancy

Inezhi forbidden to appoint pregnant. There is no clinical information regarding the use of drugs in pregnant women.

Information regarding whether the active elements of the drug are excreted along with the mother's milk is not available. Because of this, it is not used for breastfeeding.

Contraindications

Main contraindications:

• the presence of strong sensitivity in relation to drug elements;
• exacerbated liver diseases;
• an unknown, prolonged increase in transaminase levels within serum;
• combination with potent substances that inhibit the activity of the CYP3A4 enzyme (for example, ketoconazole, voriconazole and itraconazole with posaconazole, and in addition, telithromycin, clarithamycin with erythromycin, telaprevir with bocetprevir, and nephazodone with HIV protease, with a cell protease with a protease inhibitor, and with a cell protease with an HIV protease inhibitor and with the protease inhibitor and with the protease inhibitor with HIV proteasin, and also with HIV proteasin, and with erythromycin;
• combination with cyclosporine, gemfibrozil or danazol.

Side effects Inedji

The use of medicinal substances can lead to the development of adverse symptoms:

• disorders of the lymph and hematopoietic system: anemia or thrombocytopenia;
• Disorders of the National Assembly: memory loss or polyneuropathy;
• lesions of the respiratory system, mediastinum and sternum: dyspnea, cough or interstitial lung disease;
• manifestations in the gastrointestinal tract: gastritis, constipation or pancreatitis;
• signs associated with the subcutaneous layer and epidermis: IEE or alopecia, and in addition symptoms of intolerance, including urticaria, rashes, angioedema and anaphylaxis;
• disorders of the connective and musculoskeletal tissues: muscle spasms, myopathy (including myositis), and besides rhabdomyolysis (accompanied by acute renal failure or not) and tendinopathy, which is sometimes complicated by a fracture;
• nutritional and metabolic disorders: loss of appetite;
• vascular lesions: an increase in blood pressure and flushing;
• systemic signs: pain;
• problems with the work of the GP and liver: insufficiency of the liver function, jaundice, hepatitis or cholecystitis;
• lesions of the genitals: impotence;
• mental disorders: insomnia or depression.

Occasionally, there may be marked intolerance syndrome, manifested by the following symptoms: dermatomyositis, angioedema, drug lupus, polymyalgia of a rheumatic nature and vasculitis. In addition, this list includes eosiophilia, arthralgia, thrombocytopenia, arthritis, dyspnea, increased ESR, hot flushes, urticaria, fever, photosensitivity, and anxiety.

Indications of laboratory tests may change: the ALP index increases or the values of liver activity change.

Statins, including simvastatin, increase HbA1c, and in addition, the blood values of sugar.

Occasionally, cognitive disorders (state of forgetfulness, memory loss or deterioration, amnesia, and a feeling of confusion) appeared, caused by the use of statins. These disorders are often mild and treatable after withdrawal of the drug.

The use of statins can also cause additional negative manifestations: sleep disorders (there may be nightmares), impaired sexual function, diabetes mellitus (the frequency of its development is determined by the presence of risk factors (blood values of fasting sugar are ≥5.6 mmol / l, and weight index equal to ≥30 kg / m ²; in addition, increased blood pressure and increased values of triglycerides)).

[1]

Overdose

In case of poisoning with medication, supportive and symptomatic measures are performed.

Interactions with other drugs

The use of medication (especially in large portions) together with powerful substances that slow down the action of CYP3A4 (for example, ketoconazole, itraconazole, and also telithromycin, erythromycin with nefazodone, clarithromycin and HIV protease inhibitors) increases the likelihood of rhabdomyolysis or myopathy. If administration of erythromycin, itraconazole, clarithromycin, ketoconazole or telithromycin is required, use of Ineji should be canceled. Means with a powerful inhibitory effect on CYP3A4 isoenzyme, increase the likelihood of myopathy, because it interferes with the excretion of simvastatin. It is necessary to abandon the combination of drugs with other medicines, which include powerful components that slow down the activity of CYP3A4; the only exception is the situation when the probable benefit of such treatment is more expected than the risk of complications.

The combination of the drug with fenofibrate or gemfibrozil increases the plasma values of ezetimibe, respectively, by 1.5 and 1.7 times; but such an increase has no clinical significance.

Combining the drug (especially in large portions) with danazol, cyclosporine or niacin (over 1000 mg per day) also increases the likelihood of rhabdomyolysis or myopathy.

Combined use with niacin (above 1000 mg per day) should be very careful, because monotherapy with niacin can lead to myopathy.

For people using danazol or cyclosporine in a portion of more than 1000 mg per day, the dosage of the drug should be a maximum of 10/10 mg per day. It is also necessary to evaluate the possible benefits and risks of administering these medicines at the same time. When combining the drug with cyclosporine, you should regularly monitor the blood values of this component.

An increase in the likelihood of developing rhabdomyolysis or myopathy is also observed when drugs are combined with verapamil or amiodarone. There is information about the appearance of myopathy in 6% of individuals who participated in clinical tests using 80 mg of simvastatin along with amiodarone.

For individuals who use verapamil or amiodarone, the daily dose of the medication can be a maximum of 10/20 mg. Exceptions are possible only in situations where the benefits of therapy are more likely than the risk of myopathy.

In people using fusidic acid together with the drug, the probability of myopathy may increase, which is why the condition of such patients should be monitored.

Combined use with Kolestiramine resulted in a decrease in the average AUC values of total ezetimibe by about 55%. The combination of medication with this component may weaken the severity of the increasing decrease in LDL levels.

During 2 clinical tests (with healthy volunteers, as well as with persons with hypercholesterolemia), the simvastatin component in a portion of 20–40 mg per day moderately increased the effect of anticoagulants from the coumarin group, prolonging PTV indices. In this case, the initial level of MHO, which was 1.7 in volunteers, increased to 1.8, and in those with hypercholesterolemia from 2.6 to 3.4.

People who use an anticoagulant from the coumarin subgroup need to carefully monitor the blood coagulation (PTV) values before using Ineji for the first time. Further, these measurements should be carried out regularly until a stable level of MHO values is obtained. After this measurement is performed with standard intervals, which are required for control during therapy with coumarin anticoagulants. After Inegi is canceled or its dosage is changed, it is necessary to measure the blood coagulability values in an extraordinary order.

The combination of the drug with antacids leads to an insignificant decrease in the absorption of ezetimibe (the level of bioavailability of the substance remains unchanged).

As part of grapefruit juice, there are 1 or more elements that slow down the activity of CYP3A4 isoenzyme, and are able to increase the plasma values of the components whose metabolic processes occur with the participation of this isoenzyme. When using juice in small quantities (0.25 liters per day), its effect will be minimal (the activity that slows down the action of HMG-CoA reductase increases inside the blood plasma by 13%, in accordance with the indications of AUC), which has no clinical significance. But the use of juice in large volumes (more than 1 l per day) with the use of simvastatin significantly increases the intraplasma indicators of activity, which slows down the action of HMG-CoA reductase. Because of this, at the time of introduction of the drug, it is necessary to refuse to accept such juice in large volumes.

[3], [4]

Storage conditions

Ineji needs to be kept in a place that is closed to small children. The temperature range is not higher than 30 ° С.

[5]

Shelf life

Inegy can be used within a 2-year period from the time the drug is manufactured.

[6]

Application for children

The medication should not be used until the age of 10, because there is no information regarding its efficacy and drug safety for this group.

Analogs

Analogues of the medication are such means as Garlic Oil, Peponen, Pumpkin Seed Oil, Omacor with Sycod, and also Ravisol with Epadol, Revittl with Eikonol and Fish Oil.

Reviews

Inegi is a very effective drug, but it must be borne in mind that it is quite expensive.