Pharmacological action
Lipid-lowering drugs from the group of derivatives fibroevoy acid. Fenofibrate has the ability to modify the content of lipids in the human organism due to activation of receptor PPAR-α (alpha-activated receptors proliferatorom peroxisomes).
Fenofibrate increases lipolysis and elimination from the plasma of atherogenic lipoproteins with high triglyceride levels through activation of receptor PPAR-α, lipoprotein lipase and reducing the synthesis of apo C-III (apo C-III). The above effects lead to a decrease in content of fractions of LDL and VLDL, which include apo B (apo B), and increased content of HDL fraction, which include apo A-I (apo A-I) and apo A-II (apo A-II) . In addition, due to the correction of synthesis and catabolism of VLDL, fenofibrate increases LDL clearance and reduces the content of small and dense LDL particles (increase of LDL observed in patients with atherogenic lipid phenotype is accompanied by a high risk of CHD).
In clinical trials it was noted that the use of fenofibrate lowers total cholesterol by 20-25% and triglycerides by 40-55% with an increase in the level of CS-HDL by 10-30%. In patients with hypercholesterolemia, in which the level of CS-cholesterol decreased by 20-35% the use of fenofibrate resulted in a decline in the ratio: total cholesterol / HDL-XC, Hs-LPNP/Hs-LPVP, and apo B / apo A-I, which are markers of atherogenic risk.
Given the impact of fenofibrate on the level of CS-LDL and triglycerides, the use of the drug effective in patients with hypercholesterolemia as an attendant, and is not accompanied by hypertriglyceridemia, including secondary hyperlipoproteinemia, such as diabetes mellitus type 2. During treatment with fenofibrate treatment can significantly decrease or even disappear entirely extravascular deposits Xc (tendon and tuberous xanthoma). Patients with elevated levels of fibrinogen who receive treatment fenofibrate treatment, showed a significant decline in this indicator, as well as in patients with elevated levels of lipoproteins. In the treatment of fenofibrate treatment decrease the concentration of C-reactive protein and other markers of inflammation.
For patients with dyslipidemia and hyperuricemia additional advantage is that fenofibrate has urikozurichesky effect, which leads to a decrease in the concentration of uric acid by approximately 25%.
During clinical studies and animal experiments have shown that fenofibrate reduces platelet aggregation caused adrenalininduced, arachidonic acid and epinephrine.
Pharmacokinetics
Absorption
Once inside Traykora 145 mg C max achieved after 2-4 h. C max in blood plasma and the total effect of micronised fenofibrate in the form of nanoparticles (Traykor 145 mg) does not depend on the simultaneous ingestion (and therefore the drug can be taken at any time, regardless of meal).
Distribution
Fenofibroevaya acid durable and more than 99% bound to albumin plasma. T 1 / 2 - about 20 hours after the drug is not cumulative single dose and prolonged use.
Metabolism
After oral fenofibrate is rapidly hydrolyzed esterases. The plasma is found only major active metabolite of fenofibrate - fenofibroevaya acid. Prolonged use of concentration fenofibroevoy acid in the plasma remains stable, regardless of the individual patient. Fenofibrate is not a substrate for CYP3A4, is not involved in the microsomal metabolism.
Withdrawal
Derive mainly from the urine in the form fenofibroevoy acid and glucuronide conjugate. Within 6 days fenofibrate displayed almost completely.
Pharmacokinetics in special clinical situations
In elderly patients the overall clearance fenofibroevoy acid does not change.
When hemodialysis is not displayed.
Indications for use of the drug TRAYKOR
- Hypercholesterolemia and hypertriglyceridemia isolated or mixed (dyslipidemia type IIa, IIb, IV) with non-drug therapies failure (hypolipidaemic diet, weight loss, increased physical activity), especially when associated with dyslipidemia risk factors such as hypertension and smoking;
- Secondary hyperlipoproteinaemia, in cases where hyperlipoproteinaemia persists despite effective treatment of underlying disease (eg, dyslipidemia in diabetes mellitus).
Dosage regimen
Adults appoint 1 tablet 1 time /
Patients receiving 1 capsule. fenofibrate 200 mg can go to receive 1 tablet 145 mg Traykora no additional dose adjustment. Patients taking one tablet of fenofibrate 160 mg / Can go to receive 1 tablet Traykora 145 mg dose without additional adjustments.
Elderly patients are encouraged to nominate a standard dose for adults.
The use of the drug in patients with liver disease is not known.
Traykor drug 145 mg taken at any time of day, regardless of the meal, the tablet should be swallowed whole without chewing, with a glass of water.
The drug should take a long time, while continuing to diet, the patient adhered to the treatment Traykorom.
Side effect
On the part of the digestive system: (> 1 / 100, <1> 1 / 1000, <1 / 100) - pancreatitis , the formation of gallstones; (<1 / 10 000) - hepatitis. If you have symptoms of hepatitis (jaundice, pruritus) should conduct laboratory tests and, if confirmation of the diagnosis, remove the drug.
On the part of the musculoskeletal system: (> 1 / 10 000, <1 / 1000) - diffuse myalgia, myositis, muscle cramps, muscle weakness (<1 / 10 000) - rhabdomyolysis, increased CPK activity.
Since the cardiovascular system: (> 1 / 1000, <1 / 100) - deep vein thrombosis, pulmonary embolism.
On the part of the hemopoietic system: (> 1 / 10 000, <1 / 1000) - elevated levels of hemoglobin, increasing the number of leukocytes.
From the central nervous system and peripheral nervous system: (> 1 / 10 000, <1 / 1000) - sexual dysfunction, headache.
On the part of the respiratory system: (<1 / 10 000) - Interstitial pneumopathy.
From the laboratory data: (> 1 / 1000, <1 / 100) - increase the level of creatinine and urea in the blood serum.
Allergic reactions: (> 1 / 1000, <1 / 100) - skin rash, hives, itching.
Dermatological reactions: (1 / 10 000.1 / 1000) - alopecia; (<1 / 10 000) - photosensitivity, accompanied by erythema, formation of blisters or nodules on the skin areas exposed to sunlight or artificial ultraviolet light, for example, quartz lamps (these effects can occur even after months of use without any complications).
Contraindications to the use of the drug TRAYKOR
- Hepatic impairment (including cirrhosis);
- Renal failure, severe (CC <20 ml / min);
- Gallbladder disease;
- Congenital galactosemia, lactase deficiency, malabsorption of glucose and galactose (product contains lactose);
- Congenital fruktozemiya, lack sucrose-izomaltazy (product contains sucrose);
- A history of allergic reaction to peanuts, peanut butter, soy lecithin or related products (in relation to the risk of hypersensitivity reactions);
- Childhood and adolescence to 18 years;
- Lactation (breastfeeding);
- A history of photosensitivity or phototoxicity in the treatment of fibrates or ketoprofenom;
- Hypersensitivity to the drug's components.
Precautions designate patients with impaired renal function, in hypothyroidism, patients who abuse alcohol, elderly patients, with indications of a history on the hereditary muscle diseases, while taking oral anticoagulants, inhibitors of HMG-CoA reductase.
Use of the drug TRAYKOR during pregnancy and breastfeeding
Data on the use of fenofibrate in pregnancy are scarce. The potential risk for humans is unknown. Use of the drug during pregnancy is possible only when the intended benefits to the mother outweighs the potential risk to the fetus.
Due to the lack of safety data, use during lactation (breastfeeding) is contraindicated.
In experimental animal studies, teratogenic effect of fenofibrate was not found. Embryotoxicity in giving doses toxic to the maternal organism.
Application for violations of liver function
Contraindicated in hepatic failure (including cirrhosis);
Application for violations of renal function
Contraindicated in renal failure, severe (CC <20 ml / min); carefully prescribed to patients with impaired renal function
Cautions
Before you start therapy Traykorom, there should be an appropriate treatment to eliminate the cause of secondary hypercholesterolemia, for example, in diseases such as uncontrolled type 2 diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinemia, obstructive liver disease, the effects of drug therapy, alcoholism.
The effectiveness of therapy should be evaluated on the content of lipids (CH, LDL, triglycerides) in blood serum. If there is no therapeutic effect after several months of therapy (usually after 3 months) should consider whether the use of concomitant or alternative therapies.
Patients with hyperlipidemia receiving estrogens or hormonal contraceptives containing estrogen, should determine whether hyperlipidemia primary or secondary nature. In such cases, increasing lipid levels may be caused by estrogen
When you receive Traykora and other drugs that reduce the concentration of lipids, some patients described increased activity of hepatic transaminases. In most cases, this increase was temporary, minor and asymptomatic. During the first 12 months of treatment is recommended to control the level of hepatic transaminases (ALT, ACT) every 3 months. Patients who during the treatment increased the concentration of enzymes, require attention and, if elevated concentrations of alanine aminotransferase and the ACT more than 3 times compared with FHG stop taking the drug.
Have been described cases of pancreatitis during the treatment Traykorom. Possible causes of pancreatitis in these cases were: lack of efficacy in patients with severe hypertriglyceridemia, a direct effect the drug, as well as secondary effects associated with the presence of stones or the formation of sludge in the gallbladder accompanied by obstruction of the common bile duct.
When receiving Traykora and other drugs that reduce the concentration of lipids, described cases of toxic effects on muscle tissue, including the very rare cases of rhabdomyolysis. The frequency of such violations increased in the case of hypoalbuminemia and renal failure in history. The possibility of this complication increases in cases of hypoalbuminemia and renal failure.
The toxic effect on muscle tissue can be suspected based on the patient's complaints of weakness, diffuse myalgia, myositis, muscle spasms and cramps, and / or a pronounced increase in the activity of CK (more than 5 times compared to FHG). In these cases, treatment Traykorom should cease.
The risk of rhabdomyolysis may be increased in patients with a predisposition to myopathy and / or rhabdomyolysis, including age older than 70 years, weighed down by history of hereditary muscle diseases, renal failure, hypothyroidism, alcohol abuse. Such patients should be prescribed the drug only if the expected benefit exceeds the potential risk of rhabdomyolysis.
At the same time taking with inhibitors HMG-CoA reductase inhibitors or other fibrates increases the risk of serious toxic effects on muscle fibers especially if the patient prior to treatment suffered muscle diseases. In this regard, a joint appointment Traykora and statin is permissible only if the patient has severe mixed dyslipidemia and high cardiovascular risk, in the absence of a history of muscle diseases and in conditions of close monitoring to detect signs of toxic effects on muscle tissue.
In the case of increasing the concentration of creatinine by more than 50% above FHG treatment should be suspended. In the first 3 months of treatment is recommended to determine the concentration of creatinine.
Effects on ability to drive vehicles and management mechanisms
When the drug effect on the ability to drive a car and management mechanisms have been discovered.
Cases of overdose have not been described.
Treatment: the holding of symptomatic and, if necessary, supportive therapy. The specific antidote is known. Hemodialysis is ineffective.
Drug Interactions
Fenofibrate enhances the effect of oral anticoagulants and may increase the risk of bleeding, which is associated with the displacement of anticoagulant from the binding sites of plasma proteins. In the early treatment of fenofibrate treatment is recommended to reduce the dose of anticoagulants approximately one third, followed by gradual selection of the dose. Selection of the dose recommended for control of the level of MHO.
We describe a few severe cases of reversible decline of renal function during the simultaneous treatment of fenofibrate treatment and cyclosporine. It is therefore necessary to monitor the status of renal function in these patients and cancel fenofibrate in the case of a serious change in laboratory parameters.
When receiving fenofibrate together with inhibitors HMG-CoA reductase inhibitors or other fibrates increases the risk of serious toxic effects on the muscle fibers.
Studies of human liver microsomes in vitro demonstrated that fenofibrate and fenofibroevaya acid are not inhibitors isozymes CYP3A4, CYP2D6, CYP2E1 or CYP1A2. At therapeutic concentrations, these compounds are weak inhibitors of CYP2C19 and CYP2A6 isozymes, and weak or moderate inhibitors of CYP2C9.
Lipid-lowering drugs from the group of derivatives fibroevoy acid. Fenofibrate has the ability to modify the content of lipids in the human organism due to activation of receptor PPAR-α (alpha-activated receptors proliferatorom peroxisomes).
Fenofibrate increases lipolysis and elimination from the plasma of atherogenic lipoproteins with high triglyceride levels through activation of receptor PPAR-α, lipoprotein lipase and reducing the synthesis of apo C-III (apo C-III). The above effects lead to a decrease in content of fractions of LDL and VLDL, which include apo B (apo B), and increased content of HDL fraction, which include apo A-I (apo A-I) and apo A-II (apo A-II) . In addition, due to the correction of synthesis and catabolism of VLDL, fenofibrate increases LDL clearance and reduces the content of small and dense LDL particles (increase of LDL observed in patients with atherogenic lipid phenotype is accompanied by a high risk of CHD).
In clinical trials it was noted that the use of fenofibrate lowers total cholesterol by 20-25% and triglycerides by 40-55% with an increase in the level of CS-HDL by 10-30%. In patients with hypercholesterolemia, in which the level of CS-cholesterol decreased by 20-35% the use of fenofibrate resulted in a decline in the ratio: total cholesterol / HDL-XC, Hs-LPNP/Hs-LPVP, and apo B / apo A-I, which are markers of atherogenic risk.
Given the impact of fenofibrate on the level of CS-LDL and triglycerides, the use of the drug effective in patients with hypercholesterolemia as an attendant, and is not accompanied by hypertriglyceridemia, including secondary hyperlipoproteinemia, such as diabetes mellitus type 2. During treatment with fenofibrate treatment can significantly decrease or even disappear entirely extravascular deposits Xc (tendon and tuberous xanthoma). Patients with elevated levels of fibrinogen who receive treatment fenofibrate treatment, showed a significant decline in this indicator, as well as in patients with elevated levels of lipoproteins. In the treatment of fenofibrate treatment decrease the concentration of C-reactive protein and other markers of inflammation.
For patients with dyslipidemia and hyperuricemia additional advantage is that fenofibrate has urikozurichesky effect, which leads to a decrease in the concentration of uric acid by approximately 25%.
During clinical studies and animal experiments have shown that fenofibrate reduces platelet aggregation caused adrenalininduced, arachidonic acid and epinephrine.
Pharmacokinetics
Absorption
Once inside Traykora 145 mg C max achieved after 2-4 h. C max in blood plasma and the total effect of micronised fenofibrate in the form of nanoparticles (Traykor 145 mg) does not depend on the simultaneous ingestion (and therefore the drug can be taken at any time, regardless of meal).
Distribution
Fenofibroevaya acid durable and more than 99% bound to albumin plasma. T 1 / 2 - about 20 hours after the drug is not cumulative single dose and prolonged use.
Metabolism
After oral fenofibrate is rapidly hydrolyzed esterases. The plasma is found only major active metabolite of fenofibrate - fenofibroevaya acid. Prolonged use of concentration fenofibroevoy acid in the plasma remains stable, regardless of the individual patient. Fenofibrate is not a substrate for CYP3A4, is not involved in the microsomal metabolism.
Withdrawal
Derive mainly from the urine in the form fenofibroevoy acid and glucuronide conjugate. Within 6 days fenofibrate displayed almost completely.
Pharmacokinetics in special clinical situations
In elderly patients the overall clearance fenofibroevoy acid does not change.
When hemodialysis is not displayed.
Indications for use of the drug TRAYKOR
- Hypercholesterolemia and hypertriglyceridemia isolated or mixed (dyslipidemia type IIa, IIb, IV) with non-drug therapies failure (hypolipidaemic diet, weight loss, increased physical activity), especially when associated with dyslipidemia risk factors such as hypertension and smoking;
- Secondary hyperlipoproteinaemia, in cases where hyperlipoproteinaemia persists despite effective treatment of underlying disease (eg, dyslipidemia in diabetes mellitus).
Dosage regimen
Adults appoint 1 tablet 1 time /
Patients receiving 1 capsule. fenofibrate 200 mg can go to receive 1 tablet 145 mg Traykora no additional dose adjustment. Patients taking one tablet of fenofibrate 160 mg / Can go to receive 1 tablet Traykora 145 mg dose without additional adjustments.
Elderly patients are encouraged to nominate a standard dose for adults.
The use of the drug in patients with liver disease is not known.
Traykor drug 145 mg taken at any time of day, regardless of the meal, the tablet should be swallowed whole without chewing, with a glass of water.
The drug should take a long time, while continuing to diet, the patient adhered to the treatment Traykorom.
Side effect
On the part of the digestive system: (> 1 / 100, <1> 1 / 1000, <1 / 100) - pancreatitis , the formation of gallstones; (<1 / 10 000) - hepatitis. If you have symptoms of hepatitis (jaundice, pruritus) should conduct laboratory tests and, if confirmation of the diagnosis, remove the drug.
On the part of the musculoskeletal system: (> 1 / 10 000, <1 / 1000) - diffuse myalgia, myositis, muscle cramps, muscle weakness (<1 / 10 000) - rhabdomyolysis, increased CPK activity.
Since the cardiovascular system: (> 1 / 1000, <1 / 100) - deep vein thrombosis, pulmonary embolism.
On the part of the hemopoietic system: (> 1 / 10 000, <1 / 1000) - elevated levels of hemoglobin, increasing the number of leukocytes.
From the central nervous system and peripheral nervous system: (> 1 / 10 000, <1 / 1000) - sexual dysfunction, headache.
On the part of the respiratory system: (<1 / 10 000) - Interstitial pneumopathy.
From the laboratory data: (> 1 / 1000, <1 / 100) - increase the level of creatinine and urea in the blood serum.
Allergic reactions: (> 1 / 1000, <1 / 100) - skin rash, hives, itching.
Dermatological reactions: (1 / 10 000.1 / 1000) - alopecia; (<1 / 10 000) - photosensitivity, accompanied by erythema, formation of blisters or nodules on the skin areas exposed to sunlight or artificial ultraviolet light, for example, quartz lamps (these effects can occur even after months of use without any complications).
Contraindications to the use of the drug TRAYKOR
- Hepatic impairment (including cirrhosis);
- Renal failure, severe (CC <20 ml / min);
- Gallbladder disease;
- Congenital galactosemia, lactase deficiency, malabsorption of glucose and galactose (product contains lactose);
- Congenital fruktozemiya, lack sucrose-izomaltazy (product contains sucrose);
- A history of allergic reaction to peanuts, peanut butter, soy lecithin or related products (in relation to the risk of hypersensitivity reactions);
- Childhood and adolescence to 18 years;
- Lactation (breastfeeding);
- A history of photosensitivity or phototoxicity in the treatment of fibrates or ketoprofenom;
- Hypersensitivity to the drug's components.
Precautions designate patients with impaired renal function, in hypothyroidism, patients who abuse alcohol, elderly patients, with indications of a history on the hereditary muscle diseases, while taking oral anticoagulants, inhibitors of HMG-CoA reductase.
Use of the drug TRAYKOR during pregnancy and breastfeeding
Data on the use of fenofibrate in pregnancy are scarce. The potential risk for humans is unknown. Use of the drug during pregnancy is possible only when the intended benefits to the mother outweighs the potential risk to the fetus.
Due to the lack of safety data, use during lactation (breastfeeding) is contraindicated.
In experimental animal studies, teratogenic effect of fenofibrate was not found. Embryotoxicity in giving doses toxic to the maternal organism.
Application for violations of liver function
Contraindicated in hepatic failure (including cirrhosis);
Application for violations of renal function
Contraindicated in renal failure, severe (CC <20 ml / min); carefully prescribed to patients with impaired renal function
Cautions
Before you start therapy Traykorom, there should be an appropriate treatment to eliminate the cause of secondary hypercholesterolemia, for example, in diseases such as uncontrolled type 2 diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinemia, obstructive liver disease, the effects of drug therapy, alcoholism.
The effectiveness of therapy should be evaluated on the content of lipids (CH, LDL, triglycerides) in blood serum. If there is no therapeutic effect after several months of therapy (usually after 3 months) should consider whether the use of concomitant or alternative therapies.
Patients with hyperlipidemia receiving estrogens or hormonal contraceptives containing estrogen, should determine whether hyperlipidemia primary or secondary nature. In such cases, increasing lipid levels may be caused by estrogen
When you receive Traykora and other drugs that reduce the concentration of lipids, some patients described increased activity of hepatic transaminases. In most cases, this increase was temporary, minor and asymptomatic. During the first 12 months of treatment is recommended to control the level of hepatic transaminases (ALT, ACT) every 3 months. Patients who during the treatment increased the concentration of enzymes, require attention and, if elevated concentrations of alanine aminotransferase and the ACT more than 3 times compared with FHG stop taking the drug.
Have been described cases of pancreatitis during the treatment Traykorom. Possible causes of pancreatitis in these cases were: lack of efficacy in patients with severe hypertriglyceridemia, a direct effect the drug, as well as secondary effects associated with the presence of stones or the formation of sludge in the gallbladder accompanied by obstruction of the common bile duct.
When receiving Traykora and other drugs that reduce the concentration of lipids, described cases of toxic effects on muscle tissue, including the very rare cases of rhabdomyolysis. The frequency of such violations increased in the case of hypoalbuminemia and renal failure in history. The possibility of this complication increases in cases of hypoalbuminemia and renal failure.
The toxic effect on muscle tissue can be suspected based on the patient's complaints of weakness, diffuse myalgia, myositis, muscle spasms and cramps, and / or a pronounced increase in the activity of CK (more than 5 times compared to FHG). In these cases, treatment Traykorom should cease.
The risk of rhabdomyolysis may be increased in patients with a predisposition to myopathy and / or rhabdomyolysis, including age older than 70 years, weighed down by history of hereditary muscle diseases, renal failure, hypothyroidism, alcohol abuse. Such patients should be prescribed the drug only if the expected benefit exceeds the potential risk of rhabdomyolysis.
At the same time taking with inhibitors HMG-CoA reductase inhibitors or other fibrates increases the risk of serious toxic effects on muscle fibers especially if the patient prior to treatment suffered muscle diseases. In this regard, a joint appointment Traykora and statin is permissible only if the patient has severe mixed dyslipidemia and high cardiovascular risk, in the absence of a history of muscle diseases and in conditions of close monitoring to detect signs of toxic effects on muscle tissue.
In the case of increasing the concentration of creatinine by more than 50% above FHG treatment should be suspended. In the first 3 months of treatment is recommended to determine the concentration of creatinine.
Effects on ability to drive vehicles and management mechanisms
When the drug effect on the ability to drive a car and management mechanisms have been discovered.
Cases of overdose have not been described.
Treatment: the holding of symptomatic and, if necessary, supportive therapy. The specific antidote is known. Hemodialysis is ineffective.
Drug Interactions
Fenofibrate enhances the effect of oral anticoagulants and may increase the risk of bleeding, which is associated with the displacement of anticoagulant from the binding sites of plasma proteins. In the early treatment of fenofibrate treatment is recommended to reduce the dose of anticoagulants approximately one third, followed by gradual selection of the dose. Selection of the dose recommended for control of the level of MHO.
We describe a few severe cases of reversible decline of renal function during the simultaneous treatment of fenofibrate treatment and cyclosporine. It is therefore necessary to monitor the status of renal function in these patients and cancel fenofibrate in the case of a serious change in laboratory parameters.
When receiving fenofibrate together with inhibitors HMG-CoA reductase inhibitors or other fibrates increases the risk of serious toxic effects on the muscle fibers.
Studies of human liver microsomes in vitro demonstrated that fenofibrate and fenofibroevaya acid are not inhibitors isozymes CYP3A4, CYP2D6, CYP2E1 or CYP1A2. At therapeutic concentrations, these compounds are weak inhibitors of CYP2C19 and CYP2A6 isozymes, and weak or moderate inhibitors of CYP2C9.
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