Rosulip Plus caps 10mg + 10mg #30

Instruction for Rosulip Plus

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Rosulip Plus is a combined hypolipidemic agent.

Release form and composition

Rosulip Plus is produced in the form of capsules (5 + 10 mg, 10 + 10 mg and 20 + 10 mg): gelatinous solid, CONI-SNAP size No. 0, self-closing, with a base of white (5 + 10 mg) or yellow (10 + 10 mg and 20 + 10 mg) color, and a yellow lid (5 + 10 mg and 10 + 10 mg) or pale brown with a pinkish tinge (20 + 10 mg). Capsule content: 1 tablet of rosuvastatin - oblong, almost white or white, on one side engraved with the stylized letter "E" and "595" (5 mg), "596" (10 mg) or "597" (20 mg), odorless or almost odorless + 1 tablet of ezetimibe (10 mg) - round, flat, almost white or white, with a bevel, on one side engraved with the stylized letter "E", on the other - "612", without or almost odorless ( 10 capsules in a blister, in a cardboard box 3, 6 or 9 blisters and instructions for the use of Rosulip Plus).
Composition of 1 rosuvastatin tablet:
    active substance: rosuvastatin - 5/10/20 mg (in the form of rosuvastatin zinc - 5.34 / 10.68 / 21.36 mg);
    additional components: anhydrous colloidal silicon dioxide, microcrystalline cellulose (MCC), magnesium stearate.
Composition of 1 tablet of ezetimibe:
    active substance: ezetimibe - 10 mg;
    additional components: croscarmellose sodium, povidone K25, mannitol, hyprolose, sodium lauryl sulfate, MCC, magnesium stearate.
Rosulip Plus capsule shell: gelatin, titanium dioxide, iron dye yellow oxide (E172), additionally for 20/10 mg - iron dye red oxide (E172).

Pharmacodynamics

Rosulip Plus contains an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) - rosuvastatin and an inhibitor of cholesterol absorption (CS) - ezetimibe. Complementing the pharmacological action of each other, the components of the drug provide a decrease in the plasma level of Xc in the blood.

Rosuvastatin

Rosuvastatin is a hypolipidemic agent from the group of statins that competitively selectively inhibits the HMG-CoA reductase enzyme, which converts HMG-CoA into the Xc precursor mevalonate.
On the surface of hepatocytes, rosuvastatin increases the number of low density lipoprotein (LDL) receptors, which leads to increased uptake and catabolism, as well as inhibition of the synthesis of very low density lipoproteins (VLDL), providing a decrease in the total concentration of LDL and VLDL. It reduces the content of LDL-cholesterol, low-density lipoprotein cholesterol (non-HDL cholesterol), VLDL cholesterol, total cholesterol (HC), triglycerides (TG), VLDL-TG, apolipoprotein B (ApoB), increases the concentration of high density lipoprotein cholesterol (HDL) ) and apolipoprotein AI (Apo AI), and also reduces the ratio of ApoB / ApoAI, Chs-LDL / Chs-HDL, Chs-not-HDL / Chs-HDL, OHs / Chs-HDL.
The therapeutic effect is achieved within 7 days after the start of the course, after 14 days it is 90% of the maximum, after 21 days it reaches a maximum and then remains constant.

Ezetimibe

Ezetimibe is a representative of a new class of lipid-lowering drugs that inhibits the absorption of Xc in the intestine and demonstrates efficacy when taken orally. Its mechanism of action differs from that of other classes of lipid-lowering drugs, including bile acid sequestrants, statins, fibrates, and plant stanols.
The molecular target of ezetimibe is the transport protein Niemann-Pick Cl-Like 1 (NPC1L1), which is responsible for the absorption of Xc and phytosterols in the intestine. Localized on the apical surface of the limb enterocytes of the small intestine, ezetimibe blocks the absorption of Xc, reducing the flow of the latter into the liver from the intestine, as a result of which its reserves in the liver decrease and elimination from the blood increases. The substance does not increase the excretion of bile acids and does not suppress the production of Xc in the liver.

Pharmacokinetics

Rosuvastatin

The maximum concentration (Cmax) of rosuvastatin in plasma is observed 5 hours after oral administration, the absolute bioavailability averages 20%. The substance is biotransformed mainly by the liver. Volume of distribution (Vd) ~ 134 liters. It binds to plasma proteins, mostly albumin, by about 90%.
Since rosuvastatin is a non-core substrate with respect to isoenzymes of the cytochrome P450 system, it is converted in the liver in a limited amount (approximately 10%). The isoenzyme CYP2C9 is mainly responsible for the metabolism of the substance, to a lesser extent - CYP3A4, CYP2C19 and CYP2D6. The main derivatives of rosuvastatin include N-desmethylrosuvastatin and pharmacologically inactive lactone metabolites. The activity of N-desmethylrosuvastatin is approximately 50% lower than that of the basic substance. More than 90% of the activity to block the circulating HMG-CoA reductase is provided by rosuvastatin, the rest by its metabolites.
When Rosulip Plus is taken, an average of 90% of the dose of rosuvastatin is excreted through the intestines unchanged, the rest - by the kidneys. The half-life (T1 / 2) is ~ 19 hours, the average geometric plasma clearance is ~ 50 l / h.

Ezetimibe

After oral administration, ezetimibe is rapidly absorbed and intensely conjugated, leading to the formation of an active derivative - ezetimibe-glucuronide (phenolic glucuronide). For the latter, Cmax is reached within 1–2 hours, and for the main substance - after 4–12 hours. It is impossible to determine the absolute bioavailability of ezetimibe, since it is almost insoluble in water. Reception with food (including fatty food) did not affect its bioavailability when used in the form of tablets. Ezetimibe-glucuronide and ezetimibe interact with plasma proteins by 88–92% and 99.7%, respectively.
Ezetimibe metabolism occurs mainly in the liver and small intestine, through conjugation with glucuronide (phase II reaction) and further excretion with bile; the substance undergoes oxidative metabolism (phase I reaction) to a minimum. The concentrations of ezetimibe and ezetimibe-glucuronide (the main metabolite detected in plasma) are 10–20% and 80–90%, respectively, of the total plasma level of ezetimibe in the blood. Excretion of the total ezetimibe from the body occurs in the process of intestinal-hepatic recirculation, T1 / 2 is approximately 22 hours.

Indications for use

Rosulip Plus is recommended for use as an addition to the diet of patients with primary hypercholesterolemia (excluding heterozygous familial hypercholesterolemia).
Rosulip Plus is prescribed as a substitution therapy drug in cases where adequate control of the lipid profile has been achieved with the simultaneous use of separate drugs rosuvastatin and ezetimibe in doses that are equivalent to the corresponding doses in this combination.

Contraindications

Absolute:
    moderate / severe liver failure;
    liver disease in the active phase, including persistent or any increase in serum transaminase activity more than 3 times higher than the upper limit of normal (UHN);
    severe kidney dysfunction;
    predisposition to the appearance of myotoxic complications, myopathy;
    age under 18;
    pregnancy and lactation;
    lack of effective methods of contraception for women of childbearing potential;
    concomitant use of cyclosporine [the area under the pharmacokinetic curve (AUC) of rosuvastatin increases by about 7 times];
    hypersensitivity to any component of the drug.
Relative (it is recommended to use Rosulip Plus capsules with caution):
    conditions / diseases that exacerbate the risk of myopathy / rhabdomyolysis: hypothyroidism, renal failure, personal / family history of hereditary muscle damage and muscle toxicity during therapy with other HMG-CoA reductase inhibitors or fibrates in history (initial dose of rosuvastatin should not exceed 5 mg) ;
    conditions leading to an increase in the plasma level of rosuvastatin;
    trauma, major surgical interventions;
    severe water and electrolyte, metabolic or endocrine disorders, or uncontrolled convulsions;
    sepsis;
    history of liver disease;
    belonging to the Mongoloid race;
    age over 65;
    excessive alcohol consumption;
    combined use with fibrates, indirect anticoagulants (fluindione, warfarin).

Rosulip Plus, instructions for use: method and dosage

Rosulip Plus capsules are taken orally 1 time / day at the same time, regardless of the meal time. They need to be swallowed whole, without opening, washed down with water. During drug therapy, patients must continue to follow a cholesterol-free diet.
The recommended daily dose is 1 capsule.
Rosulip Plus is not intended for the initial course of therapy; you can start taking it only after determining the required doses of each of the active substances. In the event of a change in the doses of a fixed combination, it is also required first to carry out the appropriate selection of doses of both monocomponents.
If you need to take rosuvastatin at a dose of 40 mg, you cannot use Rosulip Plus.
After receiving drugs that enhance the excretion of bile acids, the lipid-lowering agent should be used at least 2 hours before or 4 hours after taking them.
In persons of Asian origin, an increase in the systemic effect of rosuvastatin was noted, as a result of this, patients of this ethnic group are recommended to take Rosulip Plus at an initial dose of 5 + 10 mg.

Side effects

    nervous system: often - dizziness, headache; infrequently - paresthesia; extremely rare - memory impairment, polyneuropathy; with an unknown frequency - sleep disorders (including insomnia, nightmares), peripheral neuropathy;
    endocrine system: often - diabetes mellitus; infrequently - decreased appetite;
    immune system: rarely - hypersensitivity reactions, including angioedema;
    blood and lymphatic system: rarely - thrombocytopenia;
    psyche: with an unknown frequency - depression;
    vessels: with an unknown frequency - rush of blood to the skin, arterial hypertension;
    digestive system: often - abdominal pain, constipation, bloating, nausea, diarrhea; infrequently - dry mouth, dyspepsia, gastritis, gastroesophageal reflux disease; rarely - increased activity of hepatic transaminases, pancreatitis; extremely rare - jaundice, hepatitis; with an unknown frequency - cholecystitis, gallstone disease;
    respiratory system: infrequently - cough;
    kidneys and urinary tract: extremely rare - hematuria;
    skin and subcutaneous tissues: infrequently - skin rash, pruritus, urticaria; with an unknown frequency - erythema multiforme, Stevens-Johnson syndrome;
    genitals and mammary gland: extremely rare - gynecomastia;
    musculoskeletal and connective tissue: often - myalgia; infrequently - muscle weakness, joint pain, muscle spasms, pain in the limbs, neck, back; rarely - myopathy (including myositis), rhabdomyolysis; with an unknown frequency - muscle pain, tendon lesions, sometimes complicated by rupture, immune-mediated necrotizing myopathy;
    laboratory parameters: often - increased activity of alanine aminotransferase (ALT) and / or aspartate aminotransferase (AST); infrequently - a dose-dependent increase in the plasma concentration of creatine phosphokinase (CPK) in the blood; increased activity of gamma glutamyl transferase (GGT); deviation from the norm of hepatic parameters;
    systemic reactions: often - increased fatigue, asthenia.

Overdose

There are no data on rosuvastatin overdose. In the course of studies, taking it in a daily dose of 50 mg for less than 14 days or in a dose of 40 mg for less than 56 days did not cause adverse events.
There are isolated reports of cases of overdose of ezetimibe, the adverse reactions that occurred during this were not considered serious.
In case of an overdose of Rosulip Plus, symptomatic and supportive treatment is recommended, as well as monitoring of liver function and the level of CPK activity. Hemodialysis is ineffective.

Special instructions

In case of an unexpected sensation of muscle weakness, pain or muscle spasms, especially against the background of malaise and fever, it is necessary to establish the level of CPK activity. With an activity more than 5 times higher than the ULN, or significant severity of muscle symptoms, even if the CPK level does not exceed the ULN by 5 times, therapy with Rosulip Plus should be interrupted. In case of relief of symptoms and normalization of CPK activity, taking the drug can be resumed in lower doses under the control of the condition.
In patients predisposed to myopathy, it is advisable to use rosuvastatin in an initial dose of 5 mg.
At the beginning of the course and after 3 months of receiving Rosulip Plus, it is recommended to monitor the indicators of liver activity. If it is revealed that the activity of hepatic transaminases is 3 times or more higher than the VGN, the intake should be discontinued.
In the case of using rosuvastatin, mainly at a dose of 40 mg / day, tubular proteinuria has been reported, usually transient and not indicative of acute kidney damage or progression of kidney disease. When receiving rosuvastatin at a dose of 40 mg, it is required to monitor renal function at least once every 3 months.
Against the background of statin therapy, an increase in blood glucose levels is possible. With a high risk of developing diabetes mellitus, these violations can lead to its manifestation with the further appointment of hypoglycemic therapy. At the same time, the reduction in the threat of vascular lesions with the use of statins exceeds the risk of developing diabetes mellitus, so this factor cannot be the basis for their cancellation. When taking Rosulip Plus, patients with a body mass index> 30 kg / m2, a fasting blood glucose level of 5.6–6.9 mmol / L, a history of arterial hypertension or hypertriglyceridemia, need medical supervision and systematic monitoring of biochemical parameters.

Influence on the ability to drive vehicles and complex mechanisms

Persons who drive vehicles or work with complex equipment need to be careful during therapy with Rosulip Plus due to the possible occurrence of dizziness.

Application during pregnancy and lactation

Rosulip Plus is contraindicated for pregnant and lactating women.
During the period of therapy, patients of childbearing age need to use reliable contraceptives.

Childhood use

Rosulip Plus is not prescribed to persons under 18 years of age.

With impaired renal function

In severe renal impairment (CC <30 ml / min), the use of a lipid-lowering agent is contraindicated.
Patients with mild / moderate severity (CC <60 ml / min) do not need to adjust the dose of Rosulip Plus.

For violations of liver function

With moderate / severe hepatic insufficiency (7-9 or more points on the Child-Pugh scale) or active phase of liver disease, including with persistent or any increase in serum transaminase activity (> 3 × ULN), the drug is contraindicated.
No dose adjustment is required for patients with mild liver dysfunction (5-6 points according to Child-Pugh). If you have a history of liver damage, use Rosulip Plus with caution.

Use in the elderly

People over 65 years of age should use Rosulip Plus with caution.
Patients over 70 years of age are advised to take rosuvastatin with an initial dose of 5 mg.

Drug interactions

    fenofibrate, gemfibrozil and other fibrates; nicotinic acid (at a dose> 1000 mg / day): the threat of myopathy is aggravated when combined with HMG-CoA reductase inhibitors; with the combination of ezetimibe and fenofibrate, there is a risk of gallbladder disease. Not recommended combination;
    HIV protease inhibitors (atazanavir + ritonavir): the Cmax and AUC of rosuvastatin may increase by about 7 and 3 times, respectively; simultaneous use is possible after dose adjustment of Rosulip Plus based on an assessment of the expected increase in the plasma level of rosuvastatin;
    inhibitors of carrier proteins (including the efflux transporter BCRP and the transporter of capture by liver cells OATP1B1): an increase in the content of rosuvastatin in the plasma is possible (since it is a substrate of a number of carrier proteins) and an increase in the risk of myopathy;
    isozymes of cytochrome P450: the interaction of rosuvastatin with other agents at the metabolic level is not expected with the participation of these enzymes; there is no significant interaction of rosuvastatin with ketoconazole and fluconazole, as well as ezetimibe and agents converted by isoenzymes CYP2C8, CYP2C9, CYP1A2, CYP2D6, CYP3A4 and N-acetyltransferase;
    fusidic acid: the threat of myopathy increases, including rhabdomyolysis when combined with statins; if therapy with fusidic acid is needed, Rosulip Plus must be canceled;
    cholestyramine: it is possible to weaken the sequential decrease in LDL-C, since the AUC of the total ezetimibe is reduced by 55%;
    erythromycin: decreases the AUC and Cmax of rosuvastatin by 20 and 30%, respectively, due to increased intestinal motility;
    antacids containing magnesium and aluminum hydroxide: reduce by an average of 50% the plasma level of rosuvastatin; antacids are recommended to be used 2 hours after taking Rosulip Plus;
    vitamin K antagonists (heparin and coumarin anticoagulants): an increase in the level of the international normalized ratio (INR) is possible; monitoring of INR is necessary during therapy and when the dose is reduced or when Rosulip Plus is stopped;
    oral contraceptives: the AUC of ethinyl estradiol increases by 26%, and norgestrel - by 34% when combined with rosuvastatin, this should be taken into account when choosing the dose of oral contraceptives and carrying out hormone replacement therapy (HRT); in the course of studies in women, this combination was well tolerated.

Terms and conditions of storage

Store out of the reach of children, at a temperature not exceeding 25 ° C.
Shelf life is 3 years.

Reviews

At the moment, there are no reviews on Rosulip Plus on specialized sites, so it is impossible to assess its effectiveness and disadvantages.
Experts believe that the new development of the pharmaceutical company "EGIS", which entered the Russian market in 2019, allows a greater number of patients to reach the target level of LDL cholesterol and several times faster than taking a double dose of rosuvastatin. In addition, taking it just once a day significantly increases patient adherence to therapy.

Terms of sell

You don't need a prescription to buy Rosulip Plus.