Mibefen NT 145 Hasan Triglyceride Triglyceride is severe (3 blisters x 10 tablets)

code: C10AB05.

fenofibrat is a derivative of fibric acid that has the effect of lowering blood lipids in humans.

Fenofibrat indirectly affects the activation of the alpha peroxisom proliferation (PPARA), increasing the process of lipid decomposition and eliminating triglycerides-rich sub-fertilizers that can cause atherosclerosis in plasma by activating lipoprotein lipase and reducing Apoprotein C-III synthesis. Activating PPARA can also increase the synthesis of A-I and A-II apoproteins.

These effects of fenofibrat on lipoprotein lead to reducing the ratio of VLDL and LDL containing Apoprotein B and increasing the HDL ratio containing Apoprotein A-I and A-II. In addition, by adjusting the synthesis and catabolic process VLDL, Fenofibrat increases LDL clearance and reduces LDL levels. LDL concentration usually increases in patients at risk of coronary artery disease.

In clinical studies, fenofibrat reduces the total cholesterol levels of 20-25%, reduces triglycerides by 40 - 55%and increases HDL -cholesterol levels by 10 - 30%. Patients with hypercholesterol hypercoleners with LDL-cholesterol levels have been reduced by 20-35%, the whole effect on cholesterol reduces the ratio of total cholesterol/HDL-Cholesterol, LDL-cholesterol/HDL-Cholesterol or APO B/APOA-I (are signs of atherosclerosis).

Fenofibrat shows a decrease in coronary events, but does not reduce the mortality rate due to all causes in preventing primary and secondary cardiovascular disease.

Condensation of cholesterol outside vessels (tendons and tumors) can be significantly reduced or even completely removed when treated with fenofibrat.

Patients with high fibrinogen levels are treated with fenofibrat, showing this parameter significantly reduced as well as for those with high LP (A) concentration. Inflammation substances such as CRP decreased when treated with fenofibrat.

Fenofibrat increases the excretion of uric acid through urine, reducing uric acid levels by about 25%, which is more beneficial for patients with blood lipid disorders with hyperuricemia.

fenofibrat has been shown to have anti -platelet aggregation effects in animal and in a clinical study (platelet reduction due to ADP, arachidonic and epinephrin).

Dynamic pharmacokinetics

Mibefen NT is a film tablet containing 145 mg of nano nano beads (nanoparticles).

absorption: fenofibrat is well absorbed in the digestive tract. The maximum concentration in plasma (CMAX) reaches 2-4 hours after taking the drug. The concentration of drugs in plasma is stable when treated continuously in all individuals. The peak concentration in plasma and the entire exposure of the nanoparticles does not depend on the meal. Therefore, it is possible to take the medicine regardless of the meal.

distribution: about 99% fenofibrat in the blood linked to plasma albumin.

metabolism: After taken, fenofibrat is quickly hydrolyzed by esterase into active metabolites of fenofibric acid, mainly associated with glucuronic acid. Fenofibrat does not metabolize through the liver microsom. There is no metabolic form in plasma. Fenofibrat is not the substrate of CYP3A4.

excretion: fenofibrat is eliminated through urine (60%) in the form of metabolites and feces (about 25%), all drugs are eliminated within 6 days. Fenofibrat is eliminated mainly in the form of fenofibric acid and glucuronid complex. The sale time of fenofibric acid in plasma is about 20 hours. In elderly patients, the total number of plasma clearance has not changed.

Research on dynamics after drinking single doses and continuous treatment shows that the drug is not accumulated. Fenofibrat is not eliminated by hemolysis.

Be cautious when using

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

Secondary causes of hyperlipidemia: Before considering treatment with fenofibrat, secondary causes of hyperemia such as type 2 diabetes are uncontrolled, hypothyroidism, kidney syndrome, blood protein disorders, obstructive liver disease or alcoholism should be fully treated. Secondary hyperkemia may be encountered after diuretics, beta blockers, estrogen, progestin, combined oral contraceptives, immunosuppressive drugs and protease inhibitors. In these cases, it is necessary to determine that increased blood lipids are primary or secondary (these drugs may increase lipid levels).

Liver function: Like other lipid lowering drugs, increasing the concentration of Transaminase has been observed in some patients, most cases only increase transient, few and asymptomatic. Recommended tracking Transaminase concentration every 3 months in the first 12 months of treatment and periodic treatment. Special attention should be noted for patients to increase the level of transaminase and stop treatment if the AST and ALT levels increase more than 3 times the upper limit of the normal level. When the symptoms of hepatitis (jaundice, itching) appear and diagnosis is determined through tests, should be discontinued with fenofibrat.

Pancreatitis: has been reported in patients using fenofibrat, may be related to treatment failure in patients with serious hyperglyceride blood, or a direct effect of the drug or secondary phenomenon through the formation of stones/sediments in biliary tract due to common bile duct obstruction.

muscle: muscle poisoning, including rare cases such as pattern pattern or not accompanied by kidney failure that have been reported when using fibrats and other lipid medications. This ratio increases in the case of lowering blood albumin and impaired kidney function before. Patients are at risk of muscle disease and/ or muscular pattern, including elderly people (> 70 years old), a history of themselves or their families with genetically damaged, kidney failure, thyroid failure or drinking a lot of alcohol, which is higher than that of muscle and muscle. In these objects, it should be carefully evaluated between the benefits and the risk of treatment and fenofibrat. Muscle poisoning should be suspected in patients with signs of spreading muscle pain, muscle inflammation, cramps and muscle weakness, and/or increasing the concentration of CPK significantly (> 5 times the upper limit of normal levels). In these cases, fenofibrat should be stopped. The risk of muscle poisoning may increase when used in combination with other fibrat drugs or HMG-Coa Reductase inhibitors, especially in the case of a history of muscle disease. Therefore, the combination of drugs should be reserved for patients with serious mixed blood lipid disorders and high cardiovascular risks without a history of muscle disease. Use carefully and closely monitor the signs of muscle poisoning.

Renal failure: Mibefen NT is contraindicated for patients with severe renal impairment (see the "contraindications" section). Precautions when used for patients with mild to moderate renal failure. Dosage should be adjusted in patients with EGFR from 30 - 59 ml/min/1.73 m. Increasing serum creatinine has been reported in mono therapy patients with fenofibrat or in combination with statins. Increasing serum creatinine is often stable over time and tends to return to normal when stopping treatment, there is no evidence that serum creatinine continues to increase when long -term treatment. In clinical trials, 10% of patients use coordination of fenofibrat and simvastatin compared to 4.4% of patients using single simvastatin with increased creatinine> 30 pmol/l compared to the basic level. 0.3% of patients undergoing treatment with increased creatinine> 200 umol/l are clinically significant. Treatment should be discontinued if creatinine concentration is 50% higher than normal. Recommendations to monitor creatinine concentration in the first 3 months after the beginning of treatment and periodically.

Preparations containing lactose: Patients with rare genetic problems in tolerance Galactose, Lapp Lactase deficiency or absorbent glucose - Galactose should not use this drug.

The effect of the drug on driving and operating machinery

fenofibrat does not affect or affect the ability to drive and operate machinery.

Use drugs for women during pregnancy and lactation

Pregnant women

There is no available data on drug use for pregnant women. Animal research does not see teratogenic effects. The toxic effect on the embryo has been observed in doses equivalent to the doses of toxicity to the mother. The potential risk on people is unknown. Therefore, only fenofibrat during pregnancy after careful assessment of benefits and risks.

breastfeeding women

It is unclear whether fenofibrat and metabolites are excreted into human milk or not. The risk for breastfed babies cannot be excluded. Therefore, Fenofibrat should not be used during breastfeeding.

Interactive drug

anticoagulant, orally (Warfarin): Fenofibrat increases the effects of oral anticoagulant drugs and may increase the risk of bleeding (prolonged PT/INR). It is recommended to reduce oral anticoagulant dose (about 1/3 of the dose to start treatment and adjust the dose slowly if necessary based on Inr monitoring).

Bile acid -mounted plastic (cholestyramin, colestipol): reduce fenofibrat absorption (take at least 1 hour ago or 4–6 hours after using bile acid -mounted plastic).

Cyclosporin: Cases of severe but recovery kidney failure have been reported when used simultaneously fenofibrat and cyclosporin. Kidney function should be closely monitored and stop treatment with fenofibrat in the case of significant changing test indicators.

HMG-CAA Reductase inhibitors (Statin) or other fibrats: Increased risk of serious muscle poisoning if used in combination with fenofibrat. Be cautious when coordinating and closely monitoring signs of muscle poisoning.

Glitazon: Some of the negative decreases with HDL-cholesterol recovery have been reported when using Fenofibrat combination with Glitazon. Therefore, it is recommended to monitor the concentration of HDL-cholesterol when combining the drug and stop one of the two drugs if the HDL-cholesterol concentration is too low.

Cytochrom P450 enzyme: In vitro studies on the liver microsom shows that fenofibrat and fenofibric acid do not inhibit CYP3A4, CYP2D6, CYP2E1 or CYP1A2; weak inhibitors CYP2C19 and CYP2A6; Mild inhibition to medium CYP2C9 at treatment concentration. Patients use fenofibrat combination with metabolic drugs through CYP2C19, CYP2A6 and especially CYP2C9 with narrow treatment index should be carefully monitored and recommended to adjust the dose if necessary.