Certificate of conformity (COC) Roxera pills 5mg, 90pcs

Roxera pills 5mg, 90pcs

$91.0

Active ingredient:	Rosuvastatin
Dosage form:	Pills

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Categories: Atherosclerosis, Medication, Metabolism

Description
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Composition

1 film-coated tablet,5 mg / 10 mg / 15 mg / 20 mg/30 mg / 40 mg contains:

Core:

Active ingredient:

Rosuvastatin Calcium 5.21 mg/10.42 mg/15.62 mg/20.83 mg/31.25 mg/41.66 mg, equivalent to Rosuvastatin 5.00 mg/10.00 mg/15.00 mg/20.00 mg/30.00 mg/40.00 mg

Auxiliary substances:

Microcrystalline cellulose, lactose, crospovidone, colloidal silicon dioxide, magnesium stearate

Film shell:

Butylmethacrylate, dimethylaminoethylmethacrylate and methyl methacrylate copolymer [1: 2: 1], macrogol-6000, titanium dioxide, lactose monohydrate

Pharmacological action

hypolipidemic agent-HMG-CoA reductase inhibitor

Indications

Primary hypercholesterolemia according to the Fredrickson classification (type IIa, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb) – as an adjunct to diet, when diet and other non-drug treatments (for example, exercise, weight loss) are insufficient.

* Familial homozygous hypercholesterolemia-as a supplement to diet and other lipid-lowering therapy (for example, LDL apheresis) or in cases where such therapy is not effective enough.

* Hypertriglyceridemia (type IV according to the Fredrickson classification) – as an adjunct to the diet.

* To slow the progression of atherosclerosis – as an adjunct to diet in patients who are indicated for therapy to reduce the plasma concentration of total cholesterol and LDL-C.

· Primary prevention of major cardiovascular complications (stroke, myocardial infarction, arterial revascularization) in adult patients without clinical signs of coronary heart disease, but with an increased risk of its development (the age of 50 years for men and over 60 years for women, increased plasma concentration of C-reactive protein [≥ 2 mg/l] in the presence of at least one additional risk factors such as hypertension, low plasma concentrations of HDL-C, Smoking, family history of early CHD).

Use during pregnancy and lactation

Roxera® is contraindicated during pregnancy and lactation.

Women of reproductive age should use adequate methods of contraception.

Since cholesterol and substances synthesized from cholesterol are important for fetal development, the potential risk of HMG-CoA reductase inhibition for the fetus exceeds the benefit of using the drug during pregnancy for the mother.

If pregnancy occurs during therapy, the use of the drug should be stopped immediately.

There are no data on the penetration of rosuvastatin into breast milk (it is known that other HMG-CoA reductase inhibitors can enter breast milk), so the use of the drug should be discontinued during breastfeeding.

Contraindications

Hypersensitivity to rosuvastatin and/or any of the excipients in the composition of the drug;
liver disease in the active phase (including a persistent increase in activity of “hepatic” transaminases and increased activity of “liver” transaminases in the serum of more than 3 times compared with the upper limit of normal);
renal failure of moderate and severe (CC less than 60 ml/min);
myopathy;
the simultaneous use of cyclosporine;
patients predisposed to the development myotoxicity complications;
pregnancy, lactation;
use in women with preserved reproductive potential who are not using adequate contraceptive methods;
hypothyroidism;
muscle disease in history (including family history);
myotoxicity the use of other inhibitors of HMG-COA reductase inhibitors or fibrates in history;
excessive alcohol consumption;
status, which may lead to increased concentrations of rosuvastatin in plasma;
the simultaneous use of fibrates;
lactose intolerance, lactase deficiency, a syndrome of glucose-galactose malabsorption;
patients of the Mongoloid race;
the age of 18.

Side effects

AES observed with rosuvastatin are usually mild and resolve on their own. As with other HMG-CoA reductase inhibitors, the incidence of AE is mainly dose-dependent.

Classification of the incidence of AE recommended by the World Health Organization (WHO):

very common ≥ 1/10

common ≥ 1/100 to < 1/10

uncommon ≥ 1/1000 to < 1/100

rare ≥ 1/10000 to < 1/1000

very rare < 1/10000

frequency unknown cannot be estimated based on available data.

Disorders of the blood and lymphatic system

frequency unknown: thrombocytopenia.

Immune system disorders

rare: hypersensitivity reactions, including angioedema.

Endocrine disorders

are common: type 2 diabetes mellitus.

Nervous system disorders

common: headache, dizziness;

very rare: memory loss or loss;

frequency unknown: peripheral neuropathy.

Respiratory, thoracic and mediastinal

disorders frequency unknown: cough, shortness of breath.

Gastrointestinal disorders

common: constipation, nausea, abdominal pain;

rare: pancreatitis;

very rare: jaundice, hepatitis;

frequency unknown: diarrhea.

When using rosuvastatin, a dose-dependent increase in the activity of “hepatic” transaminases in blood plasma is observed in a small number of patients. In most cases, it is minor, asymptomatic, and temporary.

Skin and subcutaneous tissue disorders

uncommon: pruritus, skin rash, urticaria;

frequency unknown: Stevens-Johnson syndrome.

Musculoskeletal and connective tissue

disorders common: myalgia;

rare: myopathy (including myositis), rhabdomyolysis (with or without acute renal failure);

very rare: arthralgia;

frequency unknown: immune-mediated necrotizing myopathy.

A dose-dependent increase in plasma creatine phosphokinase (CPK) activity is observed in a small number of patients taking rosuvastatin. In most cases, it is minor, asymptomatic, and temporary. If the activity of CPK in blood plasma increases more than 5 times higher than the upper limit of normal, therapy should be suspended.

Renal and urinary tract

disorders very rare: hematuria.

Proteinuria may occur in patients receiving rosuvastatin therapy. A change in the amount of protein in the urine (from no or trace amounts to ++ or more) is observed in less than 1% of patients receiving 10-20 mg of rosuvastatin, and in approximately 3% of patients receiving 40 mg of rosuvastatin. A slight change in the amount of protein in the urine was observed when taking a dose of 20 mg. In most cases, proteinuria decreases or disappears during therapy and does not indicate the occurrence of acute or progressive existing kidney disease.

Genital and breast disorders

frequency unknown: gynecomastia.

General disorders and disorders at the injection site

often: asthenic syndrome;

frequency unknown: peripheral edema.

Laboratory and instrumental data

When using rosuvastatin, the following changes in laboratory parameters were also observed: hyperglycemia, increased bilirubin concentration in blood plasma, gamma-glutamyltranspeptidase activity, alkaline phosphatase in blood plasma, changes in the serum concentration of thyroid hormones.

The following AES have been reported with some HMG-CoA reductase inhibitors (statins): depression, sleep disorders, including insomnia and “nightmarish” dreams, sexual dysfunction, and increased blood glycated hemoglobin concentrations. Isolated cases of interstitial lung disease have been reported, especially with prolonged use of medications (see section “Special instructions”).

Interaction

Effect of other medications on rosuvastatin

Transport protein inhibitors

Rosuvastatin is a substrate for some transport proteins, in particular, OATP1 In 1 and BCRP. Concomitant use of drugs that are inhibitors of these transport proteins may be accompanied by an increase in the concentration of rosuvastatin in blood plasma and an increased risk of developing myopathy (see the sections “Dosage and use”, “Special instructions” and Table 3).

Cyclosporine

With the simultaneous use of rosuvastatin and cyclosporine, the AUC of rosuvastatin is on average 7 times higher than that observed in healthy volunteers (see Table 3). Concomitant use with rosuvastatin does not affect the concentration of cyclosporine in blood plasma. The use of rosuvastatin is contraindicated in patients taking cyclosporine (see section “Contraindications”).

HIV protease inhibitors

Concomitant use of HIV protease inhibitors may significantly increase rosuvastatin exposure (see table 3). Concomitant use of 20 mg rosuvastatin and a combination of two HIV protease inhibitors (400 mg lopinavir/100 mg ritonavir) is accompanied by an increase in steady-state AUC_{(0-24 h)} and_cmax of rosuvastatin by 2 and 5 times, respectively. Therefore, simultaneous use of rosuvastatin and HIV protease inhibitors is not recommended (see the section “Dosage and use” and Table 3).

Gemfibrozil and other lipid-lowering agents

Simultaneous use of rosuvastatin and gemfibrozil leads to_{a 2-fold increase in the cmax} and AUC of rosuvastatin in blood plasma (see the section “Special instructions”). Based on the specific interaction data, no pharmacokinetically significant interaction with fenofibrate is expected, and a pharmacodynamic interaction is possible. Gemfibrozil, fenofibrate, other fibrates, and lipid-lowering doses of nicotinic acid (greater than 1 g / day) increased the risk of myopathy when co-administered with HMG-CoA reductase inhibitors, possibly due to the fact that they can cause myopathy when used in monotherapy (see section “Special instructions”). Concomitant use of fibrates and rosuvastatin in a daily dose of 30 mg is contraindicated. In such patients, therapy should begin with a dose of 5 mg / day (see the sections “Contraindications”, “Method of use and doses”, “Special instructions”).

Ezetimibe

Concomitant use of rosuvastatin 10 mg and ezetimibe 10 mg was associated with an increase in rosuvastatin AUC in patients with hypercholesterolemia (see table 3). A pharmacodynamic interaction between rosuvastatin and ezetimibe, which may increase the risk of adverse reactions, cannot be excluded.

Antacids

Concomitant use of rosuvastatin and antacids containing aluminum and / or magnesium hydroxide leads to a decrease in the plasma concentration of rosuvastatin by about 50%. This effect is less pronounced if antacids are applied 2 hours after taking rosuvastatin. The clinical significance of this interaction has not been studied.

Erythromycin

Concomitant use of rosuvastatin and erythromycin resulted in a 20% decrease in rosuvastatin AUC_(0-t) and a 30% decrease in rosuvastatin C max. This interaction may occur as a result of increased intestinal motility caused by the use of erythromycin.

Cytochrome P450 isoenzymes

The results of studies conducted in vivo and in vitro showed that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. In addition, rosuvastatin is a weak substrate for this isoenzyme system. Therefore, rosuvastatin is not expected to interact with other drugs at the level of metabolism involving cytochrome P450 isoenzymes.

There was no clinically significant interaction between rosuvastatin and fluconazole (an inhibitor of the CYP2C9 and CYP3A4 isoenzymes) and ketoconazole (an inhibitor of the CYP2A6 and CYP3A4 isoenzymes).

Drug interactions that require dose adjustment of rosuvastatin (see table 3)

The dose of Roxera® should be adjusted if it is necessary to use it simultaneously with drugs that increase the exposure of rosuvastatin. If exposure is expected to increase by a factor of 2 or more, the initial dose of Roxera® should be 5 mg once a day.

The maximum daily dose of Roxera® should also be adjusted so that the expected exposure to rosuvastatin does not exceed that for a 40 mg dose taken without concomitant use of drugs that interact with rosuvastatin. For example, the maximum daily dose of Roxera® when used concomitantly with gemfibrozil is 20 mg (1.9-fold increase in exposure), with ritonavir/atazanavir-10 mg (3.1-fold increase in exposure).

Table 3

Effect of concomitant therapy on rosuvastatin exposure (AUC, data are given in descending order) – results of published clinical studies

Concomitant therapy regimen	Rosuvastatin treatment regimen	Change in rosuvastatin AUC*
Cyclosporine 75-200 mg twice daily,6 months	10 mg once daily,10 days	7.1 x increase
Regorafenib 160 mg once daily,14 days	5 mg once	3.8 x increase
Atazanavir 300 mg / ritonavir 100 mg once daily,8 days	10 mg once	3.1 x increase
Simeprevir 150 mg once a day,7 days	10 mg once	2.8 x increase
Velpatasvir 100 mg once a day	10 mg once	2.7 x increase
Ombitasvir 25 mg / paritaprevir 150 mg / ritonavir 100 mg once daily / dasabuvir 400 mg twice daily,14 days	5 mg once	2.6 x increase
Grazoprevir 200 mg / elbasvir 50 mg once a day,11 days	10 mg once	2.3 x increase
Glecaprevir 400 mg / pibrentasvir 120 mg once daily,7 days	5 mg once daily,7 days	2.2 x increase
Lopinavir 400 mg / ritonavir 100 mg 2 times a day,17 days	20 mg 1 time a day,7 days	2.1 x increase
Clopidogrel 300 mg (loading dose), then 75 mg after 24 hours	20 mg once	2-fold increase in
Gemfibrozil 600 mg 2 times a day,7 days	80 mg once	1.9 x increase
Eltrombopag 75 mg once a day,5 days	10 mg once	1.6-fold increase
Darunavir 600 mg / ritonavir 100 mg 2 times a day,7 days	10 mg 1 time a day,7 days	1.5 x increase
Tipranavir 500 mg / ritonavir 200 mg 2 times a day,11 days	10 mg once	1.4-fold increase
Dronedarone 400 mg 2 times a day	No data available	1.4-fold increase
Itraconazole 200 mg once a day,5 days	10 mg once	**1.4-fold increase
Ezetimibe 10 mg once daily,14 days	10 mg once daily,14 days	**1.2 x increase
Fosamprenavir 700 mg / ritonavir 100 mg 2 times a day,8 days	10 mg once	No changes
Aleglitazar 0.3 mg,7 days	40 mg,7 days	No changes
Silymarin 140 mg 3 times a day,5 days	10 mg once	No changes
Fenofibrate 67 mg 3 times a day,7 days	10 mg,7 days	No changes
Rifampicin 450 mg once a day,7 days	20 mg once	No changes
Ketoconazole 200 mg 2 times a day,7 days	80 mg once	Unchanged
Fluconazole 200 mg once a day,11 days	80 mg once	No changes
Erythromycin 500 mg 4 times a day,7 days	80 mg once	20% reduction
Baikalin 50 mg 3 times a day,14 days	20 mg once	47% reduction

*The data presented as multiple changes represent a simple ratio between concomitant use and use of rosuvastatin alone. The data presented as changes in% represent the difference in% of concomitant use compared to the use of rosuvastatin alone.

**Several studies have been conducted to study the interaction of different doses of rosuvastatin, the table shows the most significant change.

Effect of rosuvastatin on other medications

Vitamin K Antagonists

As with other HMG-CoA reductase inhibitors, starting rosuvastatin therapy or increasing its dose in patients taking concomitant vitamin K antagonists (for example, warfarin) may lead to an increase in the international normalized ratio (MHO). Discontinuation of rosuvastatin or reduction of its dose may lead to a decrease in MHO. In such cases, MHO monitoring is recommended.

Oral contraceptives/Hormone replacement therapy (HRT)

Concomitant use of rosuvastatin and oral contraceptives increases the AUC of ethinyl estradiol and norgestrel by 26% and 34%, respectively. Such an increase in blood plasma concentration should be taken into account when selecting the dose of hormonal contraceptives.

Pharmacokinetic data on the concomitant use of rosuvastatin and HRT are not available, therefore, it is impossible to exclude a similar effect when using this combination. However, this combination was widely used during clinical trials and was well tolerated by patients.

Other medicinal products

No clinically significant interaction of rosuvastatin with digoxin is expected.

Fusidic acid

The risk of developing myopathy, including rhabdomyolysis, may be increased with simultaneous use of systemic fusidic acid and statins. The mechanism of this interaction (pharmacodynamic or pharmacokinetic, or both) is still unknown. There have been reports of rhabdomyolysis (including fatal outcomes in some cases) in patients receiving concomitant statins and fusidic acid.

If systemic fusidic acid is necessary, rosuvastatin therapy should be discontinued for the entire period of fusidic acid use.

How to take it, course of use and dosage

Inside, the tablet should not be chewed or crushed, swallowed whole, washed down with water, it can be taken at any time of the day, regardless of the time of food intake.

Before starting therapy with Roxera®, the patient should begin to follow a standard hypocholesterolemic diet and continue to follow it during treatment. The dose of the drug should be selected individually, depending on the goals of therapy and the therapeutic response to treatment, taking into account national recommendations for target concentrations of lipids in blood plasma.

The recommended starting dose of Roxera® for patients starting to take the drug, or for patients transferred from taking other HMG-CoA reductase inhibitors, should be 5 or 10 mg 1 time per day.

When the drug is co-administered with gemfibrozil, fibrates, nicotinic acid in lipid-lowering doses (more than 1 g / day), patients are recommended an initial dose of 5 mg/day.

When choosing the initial dose, you should be guided by the individual concentration of cholesterol in the blood plasma and take into account the possible risk of developing cardiovascular complications, as well as the potential risk of adverse reactions (AES). If necessary, the dose can be increased after 4 weeks.

Due to the possible development of AES when using a dose of 40 mg/day compared to lower doses of the drug, increasing the dose to a maximum of 40 mg/day should only be considered in patients with severe hypercholesterolemia and at high risk of developing cardiovascular complications (especially in patients with familial hypercholesterolemia), who did not achieve the desired result of therapy with a dose of 20 mg/day, and who Especially careful monitoring of patients receiving the drug at a dose of 40 mg/day is recommended.

It is not recommended to use a dose of 40 mg / day in patients who have not previously consulted a doctor. After 2-4 weeks of therapy and/or with an increase in the dose of Roxera®, monitoring of lipid metabolism parameters is necessary (if necessary, dose adjustment is required).

Patients with renal insufficiency

In patients with mild or moderate renal insufficiency, no dose adjustment is required. In patients with severe renal insufficiency (creatinine clearance less than 30 ml/min), the use of Roxera® is contraindicated. The use of Roxera® at a dose of more than 30 mg / day in patients with moderate to severe renal insufficiency (creatinine clearance less than 60 ml / min) is contraindicated. In patients with moderate renal insufficiency, the recommended starting dose of Roxera® is 5 mg / day.

Patients with hepatic insufficiency

Roxera® is contraindicated in patients with active liver disease.

Use in elderly patients

No dose adjustment is required.

Ethnic groups

In patients of the Mongolian race, an increase in systemic exposure to rosuvastatin was noted. For patients of the Mongolian race, the recommended initial dose of Roxera® is 5 mg / day, the use of Roxera® at a dose of 40 mg / day is contraindicated.

Genetic polymorphism

Carriers of the SLCO1B1 (OATR 1V1) C. 521CC and ABCG2 (BCRP) C. 421AA genotypes showed an increase in rosuvastatin AUC compared to carriers of the SLCO1B1 C. 521TT and ABCG2 C. 421CC genotypes. For patients with C. 521CC or C. 421 AA genotypes, the recommended maximum dose of Roxera® is 20 mg once a day.

Patients predisposed to myotoxic complications

The use of Roxera® at a dose of 40 mg in patients predisposed to the development of myotoxic complications is contraindicated. If doses of 10-20 mg / day are required, the recommended starting dose for this group of patients is 5 mg / day.

Concomitant therapy

Rosuvastatin binds to various transport proteins (in particular, OATP1 In 1 and BCRP). Concomitant use of Roxera with medicinal products (such as cyclosporine, certain human immunodeficiency virus (HIV) protease inhibitors, including the combination of ritonavir with atazanavir, lopinavir and / or tipranavir) that increase the concentration of rosuvastatin in blood plasma due to interaction with transport proteins may increase the risk of developing myopathy (including rhabdomyolysis). You should read the instructions for use of the above drugs before prescribing them simultaneously with Roxera®. In such cases, the possibility of alternative therapy or temporary discontinuation of Roxera should be evaluated. If the use of the above drugs is necessary, the benefit-risk ratio of concomitant therapy with Roxera® should be evaluated and the possibility of reducing its dose should be considered.

Overdose

The clinical picture of overdose is not described. The pharmacokinetic parameters of rosuvastatin do not change with simultaneous use of several daily doses of the drug.

Treatment of overdose is symptomatic and requires monitoring of liver function and serum CPK activity. There is no specific antidote. Hemodialysis is ineffective.

Description

5 mg tablets:

Round, biconvex tablets covered with a white film coating, with a chamfer and an engraving ” 5 ” applied on one side.