Epanova (Epanova)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Dosage form: & nbspcapsules
Composition:

One capsule contains:

Active substance: omega-3-carboxylic acids (omepas) * 1000 mg.

Excipients - capsule shell, gelatin (pork type A, 160 bloom) 270 mg **, sorbitol 70% (non-crystallizing) 21 mg **, glycerol 85% 105 mg **, purified water 34 mg; Capsule cover: methyl methacrylate and ethyl acrylate copolymer [1: 2], 30% dispersion *** 16 mg **, talc 17 mg, titanium dioxide 4.0 mg, iron oxide red 2.6 mg, polysorbate 80 0.32 mg, carmellose sodium 0 , 32 mg, purified water qs****, Opacode white qs [(% m / m) pharmaceutical glaze (shellac) 45% (20% esterified) in ethanol 59%, titanium dioxide 25%, butanol 13.35%, propylene glycol 1.4%, isopropanol 1.25%].

* Omega-3-carboxylic acids contain 0.3% of alpha-tocopherol.

** calculated for anhydrous substance.

*** commercial product can be used Eudragit NE 30 D.

**** Removed during production.

Description:

Red-brown oblong soft gelatin capsules coated with a coating on one side of which OME1 is printed in white. The contents of the capsules are transparent oil from yellow to yellow-brown with a specific odor.

Pharmacotherapeutic group:Lipid-lowering drug
ATX: & nbsp
  • Hypocholesterolemic and hypotriglyceridemic drugs
    • Pharmacodynamics:

    The drug Epanova contains omega-3 carboxylic acids,with the predominance of such omega-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

    Mechanism of action

    The mechanism of action of the drug is not completely understood. Potential mechanisms of action include inhibition of acyl-CoA: 1,2-diacylglycerol acyltransferase, an increase in mitochondrial and peroxisomal p-oxidation in the liver, a decrease in lipogenesis in the liver, and an increase in plasma lipoprotein lipase activity. Epanova can reduce the synthesis of triglycerides in the liver, since EPA and DHA are less active substrates for the enzymes responsible for the synthesis of triglycerides and inhibit the esterification of other fatty acids.

    Clinical Effectivecmь

    The efficacy of the Epanov preparation at a dose of 2 g and 4 g per day was evaluated in a 12-week, randomized, placebo-controlled, double-blind study involving 298 adult patients with severe hypertriglyceridemia (triglyceride level of 500-2000 mg / dl (5.6-22.6 mmol / L )).

    The drug of Epanov compared with placebo significantly reduced the concentration of triglycerides, high-density lipoprotein cholesterol (CS-non-HDL),cholesterol of very low density lipoproteins (cholesterol-VLDL), total cholesterol, while increasing the concentration of low-density lipoprotein (LDL-C) cholesterol.

    Pharmacokinetics:

    Absorption

    After ingestion, the active components of the preparation are absorbed in the small intestine, then enter the systemic circulation. When taking the drug Eganov at a dose of 4 g per day for about two weeks on a low-fat diet, the maximum concentration of total EPA in the blood plasma is reached within 5-8 hours after taking the drug, and the maximum concentration of total DHA is within 5 -9 hours. Equilibrium concentrations of EPA and DHA in blood plasma are achieved within two weeks of the daily administration of the drug Epanov.

    One-time administration of the preparation of Epanov with high-fat food resulted in an increase in the total exposure of the total and free EPA fraction, corrected relative to the baseline values, approximately 140% and 80%, respectively, compared with the use of the drug on an empty stomach. There was no change in the total exposure of the total fraction of DHA. corrected for the initial values, but there was an increase of 40% AUC (the area under the blood plasma concentration versus time curve) of the free DHA fraction corrected for the baseline values. The total exposure of the uncorrected total and free EPA fraction increased by 80% and 50%, respectively, in the absence of changes in the total exposure of the uncorrected total and free fraction of DHA.

    In clinical trials, the drug was taken regardless of food intake.

    Distribution

    After a single administration of the drug Eponov in a dose of 4 g on an empty stomach the bulk of EPA and DHA in the blood plasma is built in phospholipids, triglycerides and cholesterol esters, with a concentration of free unesterified fatty acids of approximately 0.8% and 1.1% of the total concentration of EPA and DHA, respectively.

    Metabolism and excretion

    Like the fatty acids that come with food, EPA and DHA of the drug, Epanov. are mainly subjected to oxidation in the liver. After repeated use of the drug against a background of low-fat food intake, the overall apparent plasma clearance (CL/F) and the half-life of the EPA adjusted in relation to the initial values ​​in the equilibrium state is 548 ml / h and 37 hours, respectively.Under similar conditions, the overall apparent plasma clearance and half-life of the DHA adjusted for baseline values ​​is 518 ml / h and about 46 hours, respectively.

    The drug is not excreted by the kidneys.

    Special populations of patients

    Children

    The pharmacokinetics of the drug Epanova in children has not been studied.

    Patients with impaired renal or hepatic function

    The drug was not studied in patients with impaired renal or hepatic function.
    Indications:

    The drug Epanova (omega-3-carboxylic acids) is used as part of complex therapy in adult patients with severe hypertriglyceridemia (≥ 5.6 mmol / l).

    Contraindications:

    - Hypersensitivity (eg, anaphylactic reaction) to the active substance or any of the components of the drug.

    - Age under 18 years (effectiveness and safety have not been studied).

    - Intolerance to fructose.

    - Breastfeeding period.

    Carefully:With established sensitivity to fish and / or mollusks; impaired liver function; simultaneous reception with oral anticoagulants, hemorrhagic diathesis, surgical operations (risk of increased bleeding time); pregnancy; elderly age.
    Pregnancy and lactation:

    Pregnancy

    Adequate and well-controlled studies in pregnant women have not been conducted. Studies on animals with the preparation of the drug Epawn in equivalent for human doses (in terms of body surface area) have not revealed adverse effects on pregnancy, embryo-fetal or postnatal development. During pregnancy, the drug Epanova should be used only if the potential benefit to the mother exceeds the possible risk to the fetus.

    Breastfeeding period

    It is not known whether the drug penetrates into breast milk. However, studies of omega-3 fatty acids isolated from fish oil showed excretion in breast milk of women. Influence on the development of the baby is not established. You should stop breastfeeding or stop taking Epanova, taking into account the benefits of breastfeeding for the baby and the benefits of therapy for the mother.

    Dosing and Administration:

    Inside, regardless of food intake.

    Capsules should be swallowed whole - do not break, do not grind, do not dissolve and chew; with enough water.

    Before beginning therapy with the drug, the patient should begin to observe the appropriate lipid-lowering diet and continue to observe it during treatment.

    Before the appointment of the drug, it is necessary to conduct laboratory tests to confirm a stable increase in the concentration of triglycerides. In obese patients achieve recommended lipid control serum with an appropriate diet, exercise, weight loss, as well as to achieve control of comorbidities, such as diabetes mellitus and hypothyroidism, can cause disorders of lipid metabolism. Before the appointment of medical treatment in order to reduce the concentration of triglycerides, medications that exacerbate hypertriglyceridemia (such as beta-blockers, thiazides, estrogens) should be discontinued and choose alternative therapy if possible. The recommended dose of Epanov is 2 g (2 capsules 1 g) or 4 g (4 capsules 1 g) once a day. The dose of the drug should be selected individually, depending on the therapeutic response and the tolerability of the therapy.

    Duration of treatment should be established taking into account such factors as the presence of hypertriglyceridemia and its causes.

    Application the special patents

    Children

    Safety and effectiveness of the drug in children have not been studied (see the section "Contraindications").

    Elderly patients

    Clinical experience did not reveal differences in the therapeutic effect in elderly patients and younger patients. In connection with a higher frequency of decreased liver, kidney or heart function, the presence of concomitant diseases or the use of other medications, elderly patients should carefully select the dose of the drug, starting with the minimum recommended dose.

    Side effects:

    Adverse reactions with Epanova in two clinical placebo-controlled trials of 6 and 12 weeks in patients with hypertriglyceridemia of varying severity are presented in the table below. The reactions are listed according to the following frequency: very often (≥ 1/10); often (≥ 1/100, < 1/10).

    Table. Undesirable reactions in placebo-controlled studies, noted in patients with hypertriglyceridemia, who took Epanova

    Class of organ systems Preferred term

    Frequency

    Disorders from the gastrointestinal tract

    Diarrheaa

    Often

    Nausea

    Often

    Belching

    Often

    Pain or discomfort in the abdomen

    Often

    Vomiting

    Often

    Flatulence

    Often

    Perversion of taste

    Often

    a Undesirable reactions in the form of diarrhea were mild or moderate, and were mostly resolved during the study. The incidence of diarrhea in the Epanova group of 2 g was 7%. One percent of patients discontinued therapy due to the development of diarrhea.

    In accordance with the combined data of two placebo-controlled studies of a longer duration (≥52 weeks) involving 748 patients with chronic gastrointestinal disease (376 patients took Epanov 4 g per day, 372 patients received a placebo), against the background of treatment with the drug Epanov more often than usual compared to placebo, the following frequent adverse reactions: bloating, constipation, vomiting, fatigue, nasopharyngitis, arthralgia and taste distortion.

    Overdose:

    There is no information about signs and symptoms of a possible overdose. Specific treatment for overdose does not exist. In case of an overdose, symptomatic therapy and activities aimed at maintaining the functions of vital organs and systems should be carried out.

    Interaction:

    Anticoagulants or other drugs that affect blood coagulability

    Clinical studies of the drug Epanova in patients with hypertriglyceridemia did not include patients taking antiplatelet agents or anticoagulants. AT Some published studies using omega-3 fatty acids showed an increase in bleeding time. The increase in bleeding time in these studies did not exceed the limits of normal values ​​and was not associated with episodes of clinically significant bleeding. Nevertheless, patients who take Epanova and medications that affect blood clotting (eg, antiplatelet drugs) should periodically monitor blood coagulability.

    Warfarin

    In healthy adult volunteers, the preparation of Epanov in a dose of 4 grams per day in an equilibrium state did not cause significant changes AUC or withmah (the maximum concentration in the blood plasma) R- and S-warfarin or pharmacodynamics of warfarin when taking a dose of 25 mg.

    Acetylsalicylic acid

    The concomitant use of the drug Epanova does not affect the antiplatelet effect of acetylsalicylic acid in a low dose.

    Simvastatin

    In healthy adult volunteers, the simultaneous use of simvastatin 40 mg per day and the preparation of 4 g epanov per day did not affect the exposure (AUC or withmah) simvastatin or its main active metabolite, beta-hydroxysymvastatin, in the equilibrium state.

    Rosuvastatin

    The concomitant use of the drug Epanova does not lead to significant changes in the concentration of rosuvastatin in the blood plasma.

    Research in vitro on the evaluation of inhibition of cytochrome P450 showed that the use of the preparation of Epanov in clinically significant doses does not lead to inhibition of the isozymes of the system CYP450. In vitro Epanova's drug had no effect on the protein associated with multiple drug resistance (MRP), or on the protein of resistance to breast cancer (BCRP).

    Special instructions:

    The effect of the preparation of Epanov regarding the risk of developing pancreatitis is not established. The effect of the drug Epanov on cardiovascular mortality and morbidity is not

    installed.

    Monitoring: laboratory research

    In some patients, the drug Epanova causes an increase in the concentration of LDL-C. In connection with this, during the therapy with the drug Epanov should periodically monitor the concentration of LDL-C.

    In the period of treatment with the drug Epanov in patients with impaired liver function should periodically monitor the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (ACT).

    Fish allergy

    The drug Epanova contains polyunsaturated free fatty acids, isolated from fish oil. It is not known whether the risk of developing an allergic reaction to the drug is increasing in patients with an allergy to fish and / or molluscs. The drug should be used with caution in patients with established sensitivity to fish and / or molluscs.

    Effect on the ability to drive transp. cf. and fur:

    Taking into account the safety profile, it is not expected that the preparation of Epanov will have a negative effect on the ability to drive vehicles and engage in other potentially dangerous activities that require a high concentration of attention and speed of psychomotor reactions.

    Form release / dosage:

    Capsules, 1000 mg.

    Packaging:

    For 60 capsules in a bottle of high-density polyethylene with a polypropylene twist cap with a child protection system and control the first opening. Bottle with instructions for use in a cardboard box.

    Storage conditions:

    At a temperature of no higher than 25 ° C.

    Keep out of the reach of children.

    Shelf life:

    2 years and 6 months.

    Do not use after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-004261
    Date of registration:28.04.2017
    Expiration Date:28.04.2022
    The owner of the registration certificate:AstraZeneca UK LtdAstraZeneca UK Ltd United Kingdom
    Manufacturer: & nbsp
    Representation: & nbspAstraZeneca Pharmaceuticals Ltd.AstraZeneca Pharmaceuticals Ltd.
    Information update date: & nbsp23.05.2017
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