Fenofibrate Canon, 145 mg 30 pcs

Pharmgroup:

Hypolipidemic drug.

Pharmic action:

By activating RAPP-alpha (peroxisome proliferator-activated receptor alpha), fenofibrate increases lipolysis and plasma excretion of atherogenic triglyceride-rich lipoproteins by activating lipoprotein lipase and reducing apoprotein CIII synthesis. Activation of RAPP-alpha also leads to increased synthesis of apoproteins AI and AII.

Phenofibrate is a derivative of fibric acid whose ability to change lipid content in humans is mediated by activation of RAPP-alpha. The above described effects of fenofibrate on lipoproteins lead to a decrease in the low density lipoprotein (LDL) and very low density lipoprotein (VLDL) fraction, which includes apoprotein B, and an increase in the high density lipoprotein (HDL) fraction, which includes apoproteins AI and AII.

In addition, by correction of disorders of synthesis and catabolism of HDL, fenofibrate increases clearance of LDL and reduces the content of dense and small-sized LDL particles, the increase of which is observed in patients with atherogenic lipid phenotype, a frequent disorder in patients at risk of coronary heart disease. In clinical studies it was noted that the use of fenofibrate reduces the concentration of total cholesterol by 20 – 25% and triglycerides by 40-55% while increasing the concentration of HDL-cholesterol by 10 – 30%. In patients with hypercholesterolemia whose LDL-cholesterol concentrations were reduced by 20 – 35%, use of fenofibrate resulted in lower ratios: “total cholesterol/LDL-cholesterol,” “LDL-cholesterol/LDL-cholesterol,” and “A by B/A by AI,” which are markers of atherogenic risk.

With the significant effect on LDL-cholesterol and triglyceride concentrations, fenofibrate is effective in patients with hypercholesterolemia, both accompanied and not accompanied by hypertriglyceridemia, including secondary hyperlipoproteinemia, such as in type 2 diabetes. During treatment with fenofibrate, extravascular cholesterol deposits (tendinous and tuberous xanthomas) may significantly decrease or even completely disappear. In patients with elevated levels of fibrinogen treated with fenofibrate, a significant decrease in this indicator was noted, as well as in patients with elevated levels of lipoproteins. Other inflammatory markers such as C-reactive protein also decreased with fenofibrate treatment.

For patients with dyslipidemia and hyperuricemia, an additional benefit is the uricosuric effect of fenofibrate, resulting in a decrease in uric acid concentration of approximately 25%.

Fenofibrate has been shown to reduce platelet aggregation caused by adenosine diphosphate, arachidonic acid and epinephrine in clinical studies and in animal experiments.

Pharmacokinetics:

Phenofibrate Canon in the form of micronized fenofibrate has higher bioavailability.
The original fenofibrate is not detectable in plasma. The main plasma metabolite is fenofibroic acid.

Intake:
Cmax is reached 4-5 hours after oral administration. With long-term use the concentration of the drug in plasma remains stable. Absorption of fenofibrate is enhanced with concomitant use with food.

Distribution:
Fenofibroic acid is firmly bound to plasma albumin (more than 99%).
Half-life: T1/2 of fenofibroic acid is about 20 hours.

Metabolism and excretion:
only the main metabolite of fenofibrate – fenofibroic acid is detected in blood plasma. Fenofibrate is not a substrate for CYP3A4 isoenzyme. It does not participate in microsomal metabolism.

Extracted mainly by the kidneys as fenofibroic acid and conyogate glucuronide. Within 6 days fenofibrate is eliminated almost completely. Total clearance of fenofibroic acid determined in elderly patients does not change.
The drug does not cumulate after single administration and with long-term use. It is not excreted in hemodialysis.

Indications

– combined therapy with HMG-CoA reductase inhibitors (statins) of mixed dyslipidemia (type ІІа, llb according to Fredrickson), in order to reduce triglycerides (TG) and increase HDL concentration in patients with CHD or with high risk of CHD (other clinical forms of atherosclerotic disease: Peripheral arterial atherosclerosis, abdominal aortic aneurysm and symptomatic carotid atherosclerosis; diabetes mellitus; multiple risk factors that correspond to a 10-year risk of coronary complications > 20%);

– to lower TG concentration in patients with severe hyperglyceridemia (Fredrickson type IV, V dyslipidemia);

– for the purpose of reducing elevated concentrations of LDL, total cholesterol, triglycerides and apoB (apolipoprotein B) and increasing concentrations of HDL in patients with primary hyperlipidemia or mixed dyslipidemia (Fredrickson type Ia, llb, III, IV).

Active ingredient

Composition

1 tablet:

– fenofibrate 145 mg

Supplementary substances:

corn starch – 137 mg,

colloidal silicon dioxide – 10 mg,

croscarmellose sodium – 33 mg,

p> mannitol – 170 mg,

magnesium stearate – 6 mg,

povidone K-30 – 44 mg,

microcrystalline cellulose – 105 mg.

Composition of the film coating:

Opadray II white – 20 mg, including polyvinyl alcohol – 9.38 mg,

macrogol – 4.72 mg,

talc – 3.48 mg,

titanium dioxide – 2.42 mg.

How to take, the dosage

The tablets should be swallowed whole, without chewing, at the same time as a meal.

Adults:
One tablet once daily. Patients taking one capsule of fenofibrate 200 mg can switch to taking one tablet of the drug Fenofibrate Canon 145 mg without additional dose adjustments. The maximum daily dose is 145 mg.

Elderly patients:
It is recommended to take 1 tablet of 145 mg for adults (one tablet once daily).

Patients with liver disease:
The use of the drug in patients with liver disease has not been studied.

The drug should be taken for a long time, while continuing to follow the diet that the patient followed before treatment with Fenofibrate Canon.

Interaction

Peroral anticoagulants:

Fenofibrate increases the effect of oral anticoagulants and may increase the risk of bleeding, which is associated with displacement of anticoagulant from binding sites with plasma proteins.

At the beginning of treatment with fenofibrate, it is recommended to reduce the dose of anticoagulants by approximately one-third, with a subsequent gradual adjustment of the dose. Dose adjustment is recommended while monitoring the INR (international normalized ratio) level.

Cyclosporine:
Several severe cases of reversible reduction in renal function during concomitant treatment with fenofibrate and cyclosporine have been described. Therefore, it is necessary to monitor the status of renal function in such patients and to cancel fenofibrate in case of serious changes in laboratory parameters.

HMG-CoA reductase inhibitors (statins) and other fibrates:

The use of fenofibrate concomitantly with HMG-CoA reductase inhibitors or other fibrates increases the risk of serious toxic effects on muscle fibers (see section “Special Precautions”).

Cytochrome P450 system isoenzymes:

In vitro studies of human liver microsomes have shown that fenofibrate and fenofibroic acid are not inhibitors of the following cytochrome P450 isoenzymes (CYP3A4, CYP2D6, CYP2E1 or CYP1A2). In therapeutic concentrations, these compounds are weak inhibitors of CYP2C19 and CYP2A6 isoenzymes and weak or moderate inhibitors of CYP2C9.

Special Instructions

Before initiating treatment with Fenofibrate Canon, appropriate treatment should be performed to eliminate the cause of secondary hypercholesterolemia, for example, in diseases such as uncontrolled type 2 diabetes, hypothyroidism, nephrotic syndrome, dysproteinemia, obstructive liver disease, consequences of drug therapy, alcoholism.

The effectiveness of therapy should be evaluated by the content of lipids (total cholesterol, LDL, triglycerides) in blood serum. If there is no therapeutic effect after several months of therapy (usually after 3 months), consideration should be given to prescribing concomitant or alternative therapy.

In patients with hyperlipidemia who are taking estrogens or estrogen-containing hormonal contraceptives, it should be determined whether the hyperlipidemia is of a primary or secondary nature. In such cases, the increase in lipid levels may be due to estrogen intake.

Liver function: When taking fenofibrate and other lipid-lowering drugs, some patients have described an increase in liver transaminases. In most cases, such an increase was temporary, insignificant and asymptomatic. During the first 12 months of treatment, it is recommended to monitor the activity of transaminases (alanine aminotransferase (ALT), aspartate aminotransferase (ACT)) every 3 months. Patients with increased concentration of transaminases during treatment should be treated, and in case of ALT and ACT concentration increase more than 3 times in comparison with upper limit of norm the drug administration should be discontinued.

Pancreatitis: cases of pancreatitis have been described during treatment with fenofibrate. The possible causes of pancreatitis in these cases were: insufficient effectiveness of the drug in patients with severe hypertriglyceridemia, direct effect of the drug, as well as secondary events associated with the presence of stones or formation of sediment in the gallbladder accompanied by obstruction of common bile duct.

Muscles: When taking fenofibrate and other lipid-lowering drugs, cases of toxic effects on muscle tissue have been described, including very rare cases of rhabdomyolysis. The frequency of this disorder increases in the case of hypoalbuminemia and renal failure in the history. The possibility of this complication increases in cases of hypoalbuminemia and renal failure.

Toxic effects on muscle tissue may be suspected on the basis of patient’s complaints of weakness, diffuse myalgia, myositis, muscle cramps and seizures and/or a marked increase in creatinine phosphokinase (CPK) activity (more than 5 times the upper limit of normal). In these cases, treatment with fenofibrate should be stopped.

The risk of rhabdomyolysis may be increased in patients with predisposition to myopathy and/or rhabdomyolysis, including age over 70 years, history of hereditary muscle diseases, renal dysfunction, hypothyroidism, alcohol abuse. In such patients the drug should be administered only if the expected benefit exceeds the possible risk of rhabdomyolysis. When taking Fenofibrate Canon simultaneously with HMG-CoA reductase inhibitors or other fibrates, the risk of serious toxic effects on muscle fibers increases, especially if the patient had muscle disease before treatment. Therefore, co-administration of Fenofibrate Canon and statins is acceptable only if the patient has severe mixed dyslipidemia and high cardiovascular risk, if there is no history of muscle disease and under close monitoring to detect signs of developing toxic effects on muscle tissue.

Renal function: When using Fenofibrate Canon as monotherapy or in combination with statins, a reversible increase in serum creatinine concentration has been noted in patients. The increase in creatinine concentration was generally stable over time with no evidence of further increases in serum creatinine concentration during long-term therapy, with a tendency to return to initial values after treatment withdrawal. The clinical significance of these observations has not been established. In patients with renal insufficiency when taking Fenofibrate Canon, it is recommended to monitor renal function. Monitoring of renal function should be performed in patients at risk of renal failure, namely elderly patients and patients with diabetes mellitus. Treatment should be withdrawn in case of an increase in creatinine concentration > 50% of the upper limit of normal. It is recommended to determine creatinine concentration during the first 3 months after the start of treatment, and periodically after its termination.

Impact on the ability to drive and operate motor vehicles and other mechanisms:

No effect on driving and other machinery has been noted with the use of the drug.

Contraindications

– hypersensitivity to fenofibrate or other components of the drug;
– hepatic failure (including biliary cirrhosis and persistent liver dysfunction of unclear etiology);
– severe renal failure (creatinine clearance < 20 ml/min);
– age under 18 years (effectiveness and safety are not established);
– history of photosensitization or phototoxicity during treatment with fibrates or ketoprofen;
– history of gallbladder disease;
– period of breastfeeding;
– chronic or acute pancreatitis, except for cases of acute pancreatitis due to severe hypertriglyceridemia.

With caution: in hypothyroidism; patients who abuse alcohol; patients with impaired renal function (CK more than 20 ml/min); elderly patients with a history of hereditary muscle diseases; in concurrent use of oral anticoagulants, HMG-CoA reductase inhibitors (see section “Interaction with other medicinal products”).

Side effects

Side effects for therapeutic doses are given with distribution by frequency and system-organ classes according to WHO classification: very often – ≥1/10 appointments (>10%) often – ≥1/100 to <1/10 appointments (>1% and 0.1% and <1%) rarely – ≥1/10000 to <1/1000 appointments (>0.01% and Digestive system disorders:
frequent – abdominal pain, nausea, vomiting, diarrhea and moderate severity flatulence;
infrequent – cases of pancreatitis.
frequent – moderate increase in serum transaminases concentration; infrequent – formation of gallstones;
very rare – hepatitis.

In case of symptoms of hepatitis (jaundice, skin pruritus) it is necessary to perform laboratory tests and in case of confirmation of hepatitis fenofibrate should be canceled. (see section “Special indications”).

Muscular system and connective tissue disorders:
rarely – diffuse myalgia, myositis, muscle spasm and weakness;
very rarely – rhabdomyolysis, increased creatine phosphokinase (CPK) activity.

Vascular disorders:
infrequent – venous thromboembolism (pulmonary embolism, deep vein thrombosis).

Blood and lymphatic system disorders:
rarely – increase of hemoglobin and leukocytes.

Nervous system disorders:
rarely – sexual dysfunction, headache.

Respiratory system disorders:
very rarely – interstitial pneumopathy.

Skin and subcutaneous fatty tissue:
infrequent rash, skin itching, urticaria or photosensitivity reactions;
rare – alopecia;

Very rarely – photosensitization accompanied by erythema, blisters or nodules on the skin areas exposed to sunlight or artificial UV light (e.g., quartz lamp) in some cases (even after several months of use without any complications).

Laboratory studies:
infrequent – increase in serum creatinine and urea concentrations.

Overdose

No cases of overdose have been described.

A specific antidote is not known.

In case of suspected overdose, symptomatic and, if necessary, supportive treatment should be prescribed.

Hemodialysis is ineffective.

Similarities