Pharmacological action Tricor 145
Tricor Hypolipidemic agent from the group of fibric acid derivatives. Fenofibrate has the ability to modify the content of lipids in the human body by activating receptors PPAR-α (alpha receptors, peroxisome proliferator-activated).
Fenofibrate increases lipolysis and elimination of plasma atherogenic lipoproteins with high triglycerides by activating the receptor PPAR-α, lipoprotein lipase and reducing the synthesis of apoprotein C-III (apo C-III). The effects described above lead to a decrease in the content of LDL and VLDL fractions, which include the apoprotein B (apo B), and increased levels of HDL fraction, which include the apoprotein A-I (apo A-I) and apoprotein A-II (apo A-II) . In addition, due to the correction of synthesis and catabolism of VLDL, fenofibrate increases LDL clearance and reduces the amount of small, dense LDL particles (increase of LDL cholesterol observed in patients with atherogenic lipid phenotype is accompanied by a high risk of CHD).
In clinical studies, it was noted that the use of fenofibrate lowers total cholesterol by 20-25% and triglycerides by 40-55% at higher levels of HDL-C by 10-30%. In patients with hypercholesterolemia, in which the level of LDL-C decreased by 20-35% the use of fenofibrate decreased the ratios: total XC / HDL-C, apo B and Hs-LPNP/Hs-LPVP / apo A-I, which are markers of atherogenic risk.
Given the effect of fenofibrate on the level of LDL-C and triglycerides, use of the drug is effective in patients with hypercholesterolemia as accompanied or not accompanied by hypertriglyceridemia, including secondary hyperlipoproteinaemia such as diabetes mellitus type 2. During treatment with fenofibrate can significantly decrease or even disappear entirely extravascular deposition c (tendon and tuberous xanthomas). In patients with elevated levels of fibrinogen, treated with fenofibrate, a significant reduction in this indicator, as well as in patients with elevated LDL. In the treatment with fenofibrate decrease the concentration of C-reactive protein and other markers of inflammation.
For patients with dyslipidemia and hyperuricemia additional advantage is that fenofibrate exerts urikozurichesky effect, which leads to a decrease in uric acid concentration by approximately 25%.
In the clinical study and animal experiments have shown that fenofibrate reduces the platelet aggregation induced by adenosine diphosphate, arachidonic acid and epinephrine.
Pharmacokinetics Tricor 145
Absorption
After oral administration of 145 mg Tricor 145 Cmax achieved within 2-4 h. Cmax in blood plasma and micronized fenofibrate common action in the form of nanoparticles (145 mg Tricor 145) does not depend on the simultaneous reception of food (and the drug can be taken at any time, regardless of food intake .)
Distribution
Fenofibroevaya acid strongly and more than 99% bound to plasma albumin. T1 / 2 – 20 h. The drug does not accumulates after a single dose and long-term use.
Metabolism
After oral administration, fenofibrate is rapidly hydrolyzed esterases. The plasma is found only major active metabolite of fenofibrate – fenofibroevaya acid. With prolonged use concentration fenofibroevoy acid in plasma is stable, regardless of the individual patient. Fenofibrate is not a substrate for CYP3A4, is not involved in the microsomal metabolism.
Breeding
Output, mainly in the urine as fenofibroevoy acid and conjugate glucuronide. During the 6 day fenofibrate appears almost completely.
Pharmacokinetics in special clinical situations
In elderly patients the total clearance fenofibroevoy acid does not change.
When dialysis is not displayed.
Indications for use of the drug Tricor 145
- Hypercholesterolemia and hypertriglyceridemia isolated or mixed (dyslipidemia type IIa, IIb, IV) the ineffectiveness of non-drug treatments (lipid-lowering diet, weight loss, increased physical activity), especially when associated with dyslipidemia risk factors such as hypertension and smoking;
- Secondary hyperlipoproteinemia, when hyperlipoproteinaemia persists despite effective treatment of the underlying disease (eg, dyslipidemia in diabetes mellitus).
Dosage regimen Tricor 145
Adults appoint 1 tablet 1 time / day.
Patients taking 1 capsule. fenofibrate 200 mg can go on taking 1 pill Tricor 145 mg no additional dose adjustment. Patients taking one tablet of fenofibrate 160 mg / day. Can go on taking 1 pill Tricor 145 mg dose without further adjustment.
Elderly patients are encouraged to nominate a standard dose for adults.
Use of the drug in patients with liver disease is not known.
The drug is 145 mg Tricor 145 take at any time, regardless of the meal, the tablet should be swallowed whole without chewing, drinking a glass of water.
The drug should be taken for a long time, while continuing to follow a diet, which the patient adhered to the treatment Tricor 145.
Side effect Tricor 145
From the digestive system: (> 1 / 100, <1 / 10) – abdominal pain, nausea, vomiting, diarrhea, and flatulence of moderate severity, a moderate increase in liver transaminases (> 1 / 1000, <1 / 100) – pancreatitis , gallstones, (<1 / 10 000) – hepatitis. When symptoms of hepatitis (jaundice, pruritus) should be carried out laboratory tests and, if confirmation of the diagnosis, stop medication.
On the part of the musculoskeletal system: (> 1 / 10, 000, <1 / 1000) – diffuse myalgia, myositis, muscle cramps, muscle weakness (<1 / 10, 000) – rhabdomyolysis, elevated creatine kinase.
Cardio-vascular system: (> 1 / 1000, <1 / 100) – deep vein thrombosis, pulmonary embolism.
From the hemopoietic system: (> 1 / 10, 000, <1 / 1000) – increase in hemoglobin, increasing the number of leukocytes.
From the central and peripheral nervous system (> 1 / 10, 000, <1 / 1000) – Sexual dysfunction and headache.
The respiratory system (<1 / 10 000) – Interstitial pneumopathy.
From the laboratory parameters (> 1 / 1000, <1 / 100) – increase in serum 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, blistering, or nodules on the skin areas exposed to sunlight or artificial UV light, for example, quartz lamps (these effects can occur even after months of use without any complications).
Contraindications to the use of the drug Tricor 145
- Hepatic impairment (including cirrhosis);
- Renal failure, severe (creatinine clearance <20 ml / min);
- Gallbladder disease;
- Congenital galactosemia, the lack of lactase malabsorption of glucose and galactose (product contains lactose);
- Congenital fruktozemiya, failure saccharases-izomaltazy (product contains sucrose);
- A history of allergic reaction to peanuts, peanut butter, soy lecithin or related products (due to the risk of hypersensitivity reactions);
- Children and teens under 18;
- Lactation (breastfeeding);
- A history of photosensitivity or phototoxicity in the treatment of fibrates or ketoprofen;
- Hypersensitivity to the drug.
With caution in patients with impaired renal function, hypothyroidism, patients who abuse alcohol, elderly patients, with indications of a history of hereditary muscle diseases at, while receiving oral anticoagulants, inhibitors of HMG-CoA reductase inhibitors.
Use of the drug Tricor 145 in 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 effects of fenofibrate has not been detected. Embryotoxicity when administered in doses that are toxic to the mother’s body.
Use in hepatic dysfunction Tricor 145
Contraindicated in hepatic impairment (including cirrhosis);
Use in renal impairment Tricor 145
Contraindicated in severe renal insufficiency (creatinine clearance <20 ml / min) with caution in patients with impaired renal function
Cautions Tricor 145
Before you begin to care Tricor 145, 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, disproteinemia, obstructive liver disease, the effects of drug therapy, alcoholism.
The effectiveness of therapy should be evaluated on the content of lipids (XC, LDL, triglycerides) in blood serum. In the absence of therapeutic effect after several months of therapy (usually after 3 months) should consider the advisability of appointing a concomitant or alternative therapies.
Patients with hyperlipidemia receiving estrogen or hormonal contraceptives containing estrogen, should determine whether the primary or secondary hyperlipidemia nature. In such cases, improvement in lipid levels may be due to estrogen
When you receive Tricor 145 and other drugs that lower lipid concentrations, some patients described increase in liver 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 liver enzymes (ALT, ACT) every 3 months. Patients who during the treatment increased the concentration of enzymes, require attention, and in case of increasing the concentration of ALT and the ACT more than 3 times the ULN with the drug is discontinued.
Have been described cases of pancreatitis during the treatment period Tricor 145. Possible causes of pancreatitis in these cases were: lack of efficacy in patients with severe hypertriglyceridemia, a direct effect of the drug, as well as secondary effects associated with the presence of stones or sludge formation in the gall bladder, accompanied by obstruction of the common bile duct.
When you receive Tricor 145 and other drugs that lower lipid concentrations, described cases of toxic effects on muscle tissue, including the very rare cases of rhabdomyolysis. The frequency of such disorders is increased in case of hypoalbuminemia and renal failure in history. The possible occurrence of this complication increases in cases of hypoalbuminemia and renal failure.
Toxic effect on muscle tissue can be suspected on the basis of patient’s complaints of weakness, diffuse myalgia, myositis, muscle spasms and cramps, and / or increase the activity of creatine kinase expressed (more than 5 times compared to the ULN). In these cases, treatment should be discontinued Tricor 145.
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 a history of hereditary muscle disorders, renal failure, hypothyroidism, alcohol abuse. Such patients should be prescribed the drug only if the expected benefit exceeds the potential risk of rhabdomyolysis.
When concomitantly with inhibitors of 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 Tricor 145 and a statin is permissible only if the patient severe mixed dyslipidemia and high cardiovascular risk, in the absence of muscle diseases in history and in close monitoring aimed at identifying the signs of toxic effects on muscle tissue.
In the case of serum creatinine increase of more than 50% above the ULN, treatment should be suspended. In the first 3 months of treatment is recommended to determine the concentration of creatinine.
Effects on ability to drive and control mechanisms
Before the drug effect on the ability to drive a car and management mechanisms have been identified.
Overdose Tricor 145
Cases of overdosage have not been described.
Treatment: symptomatic and, if necessary, supportive therapy. Specific antidote is known. Hemodialysis is ineffective.
Drug Interactions Tricor 145
Fenofibrate increases the effect of oral anticoagulants and may increase the risk of bleeding, which is associated with the displacement of anticoagulant from the binding sites to plasma proteins. At the beginning of fenofibrate treatment is recommended to reduce the dose of anticoagulants by about a third, followed by gradual dose adjustment. Dosage recommended for control of the level of MHO.
Described several cases of severe reversible decline in kidney function during simultaneous treatment with fenofibrate and cyclosporin. It is therefore necessary to monitor the status of renal function in these patients and cancel fenofibrate in the event of serious changes in laboratory parameters.
When administered simultaneously with fenofibrate inhibitors of HMG-CoA reductase inhibitors or other fibrates increases the risk of serious toxic effects on muscle fibers.
Studies of microsomes from human liver in vitro have shown that fenofibrate and fenofibroevaya acid does not inhibit isozymes CYP3A4, CYP2D6, CYP2E1 or CYP1A2. At therapeutic concentrations, these compounds are weak inhibitors of isoenzymes CYP2C19 and CYP2A6, and mild or moderate inhibitors of CYP2C9.
