Fenofibrate - instructions for use, dose, side effects, contraindications

Metabolite fenofibrata (fenofibroevaya acid) activates the recipes PPARα and lipoproteinlipazu, enhances lipolysis and the removal of plasma atherogenic lipoproteins with a high content of triglycerides. It also leads to a decrease in the synthesis of apolipoproteins CIII and an increase in the synthesis of apolipoproteins AI and AII.

Thus, there is a decrease in the content of the fraction of LDL and VLDL, including apolipoprotein B, and an increase in the concentration of HDL, including apolipoproteins AI and AII.

Fenofibrate increases the clearance of LDL and reduces the content of dense and small particle size of LDL, the increase of which is noted in patients with atherogenic lipid phenotype (in patients with IHD risk).

The use of fenofibrate can reduce the level of total cholesterol by 20-25% and triglycerides by 40-55% with an increase in the level of HDL cholesterol by 10-30%, which leads to a decrease in atherogenic risk ..

The use of fenofibrate is advisable in patients with hypercholesterolemia, isolated or with concomitant hypertriglyceridemia, including secondary hyperlipoproteinemia, including those with type 2 diabetes mellitus. With prolonged intake reduces extravascular deposition of cholesterol.

Pharmacokinetics:

After oral administration fenofibrate is transformed into an active metabolite, fenofibroic acid, whose time in plasma is reached within 2-3 hours. Binding of fenofibric acid with plasma proteins is about 99%, equilibrium concentration is reached within 1 week. Both substances are not exposed to oxidative metabolism involving cytochrome P450. It is excreted mainly by the kidneys, the half-life period is about 20 hours. It does not cumulate.

The clearance of fenofibric acid after a single intake of fenofibrate inside, depending on the age, does not change and is about 1.1-1.2 l / h.

If the renal function of mild and moderate severity (creatinine clearance of 30-80 ml / min) increases, the half-life of fenofibroic acid increases. In patients with severe renal insufficiency (creatinine clearance <30ml / min), the exposure of fenofibric acid is increased 2.7 times, cumulation is noted with repeated admission.

Indications:Hyperlipidemia type IIa, IV and V types, as well as type IIb and III with insufficient dietary efficiency, increased cholesterol in the blood during a dynamic study and / or the presence of concomitant risk factors.

ICD-10

IV.E70-E90.E78.1 Pure hyperglyceridemia

IV.E70-E90.E78.5 Hyperlipidemia, unspecified

IV.E70-E90.E78.2 Mixed hyperlipidemia

Contraindications:Hypersensitivitytion, photosensitization or phototoxicity in the treatment of fibrates or ketoprofen in the anamnesis, hepatic insufficiency (including biliary cirrhosis), severe renal failure (creatinine clearance <30ml / min), gallbladder disease, , age to 18 years (adequate and well-controlled studies have not been conducted).

Carefully:Hepatic and / or renal failure, hypothyroidism, alcoholism, elderly age, hereditary muscle diseases in history, simultaneous administration of oral anticoagulants, inhibitors of HMG-CoA reductases.

Pregnancy and lactation:

When pregnancy is possible, if the expected effect of therapy exceeds the potential risk to the fetus.

Action category for the fetus by FDA - C.

For the duration of treatment, breastfeeding should be discontinued.

Dosing and Administration:

Inside adults - 200-400 mg per day in 3 divided doses.

Preparations containing micronized fenofibrate, appoint at the rate of 200 mg fenofibrate 1 time per day. Children - 5 mg / kg per day.

Side effects:

From the side nervous system and sense organs: dizziness, headache, fatigue.

From the side cardiovascular system and blood (hematopoiesis, hemostasis): venous thromboembolism (pulmonary embolism, deep vein thrombosis), increased hemoglobin level, leukocytosis.

From the side organs of the digestive tract: abdominal pain, nausea, vomiting, diarrhea, flatulence, pancreatitis, cholelithiasis, increased levels of hepatic transaminases and creatine phosphokinase, hepatitis.

From the side genitourinary system: acute renal failure, violation of sexual function.

From the side musculoskeletal system: myalgia, myositis, muscle spasm, muscle weakness, rhabdomyolysis.

Allergic reactions: skin rashes, itching, hives.

Other: interstitial pneumonia, photosensitization, alopecia, hypercreatinemia, increased urea in the blood plasma.

Overdose:

Symptoms: nausea, vomiting, diarrhea.

Treatment: symptomatic. The specific antidote is unknown. Hemodialysis is ineffective.

Interaction:

Fenofibrate enhances the effect of oral anticoagulants (coumarin derivatives, indanedione) and may increase the risk of bleeding, which is due to the displacement of the anticoagulant from the binding sites to plasma proteins (with caution at the same time). At the beginning of treatment with fenofibrate, it is recommended to reduce the dose of anticoagulant by approximately 1/3, followed by a gradual selection of a dose under the control of the INR level.

When taking fenofibrate concomitantly with HMG-CoA reductase inhibitors or other fibrates, the risk of rhabdomyolysis, myopathy and acute renal failure increases (combined use is not recommended). Sequestants of bile acids reduce the absorption of fenofibrate (fenofibrate should be taken 1 hour before or 4-6 hours after they are taken).

Cyclosporine - increased likelihood of nephrotoxicity.

Special instructions:

Treatment for a long time in conjunction with the hypocholesterolean diet and under the supervision of a doctor. The effectiveness of therapy should be assessed by the content of lipids (total cholesterol, LDL, triglycerides) in serum. In the absence of therapeutic effect after 3-6 months of treatment, tactics should be reviewed.

In clinical studies, 67 mg of the "micronized" form of fenofibrate is bioequivalent to 100 mg of "non-micronized" form.

It is necessary to monitor the activity of liver transaminases every 3 months in the first year of therapy; with an increase in ALT by 2 times or more, the appearance of myalgia and muscle weakness fenofibrate cancel. In the first 3 months of treatment, monitor creatinine (with increasing creatinine concentration more than 50% above the upper limit of normal treatment should be suspended).

In patients with hyperlipidemia, taking estrogens or hormonal contraceptives containing estrogens, it is necessary to determine the primary or secondary nature of hyperlipidemia.

In patients with a predisposition to myopathy and / or rhabdomyolysis, rclaim of rhabdomyolysis. Also, the risk of rhabdomyolysis is preserved in patients with a history of hereditary muscle diseases, impaired renal function, hypothyroidism, alcohol abusers and people over 70 years old.

Co-administration of fenofibrate and statins is possible only if the patient has severe mixed dyslipidemia and high cardiovascular risk, in the absence of a history of muscle disease under the strict control of the possibility of rhabdomyolysis.

Impact on the ability to drive vehicles and manage mechanisms not found.

Instructions

Fenofibrate (Fenofibratum)