Rozart pills 5mg, 90pcs

Composition

Active ingredient:

rosuvastatin 5 mg;

Auxiliary substances:

microcrystalline cellulose type 102,

crospovidone type A,

calcium hydrophosphate dihydrate,

lactose monohydrate,

magnesium stearate;

Film coating:

Opadray white II 33G28435 (hypromellose, titanium dioxide, lactose monohydrate, macrogol-3350, triacetin)

Pharmacological action

Rozart is a hypolipidemic agent from the statin group. Selective competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, an enzyme that converts HMG-CoA to mevalonate, a cholesterol precursor. Increases the number of low-density lipoprotein (LDL) receptors on the surface of hepatocytes, which leads to increased uptake and catabolism of LDL, inhibition of the synthesis of very low-density lipoproteins( VLDL), reducing the total amount of LDL and VLDL.

Reduces the elevated concentration of LDL cholesterol, low-density lipoprotein cholesterol (non – HDL), VLDL cholesterol, total cholesterol, triglycerides (TG), TG-VLDL, apolipoprotein B (ApoV), reduces the ratio of LDL-cholesterol/HDL-cholesterol, total cholesterol/HDL-cholesterol, cholesterol-non-HDL/HDL-cholesterol. HDL cholesterol, apoB/apolipoprotein A-I (ApoA-I), increases the concentration of HDL cholesterol and ApoA-I.

The hypolipidemic effect is directly proportional to the prescribed dose. The therapeutic effect appears within 1 week after the start of therapy, after 2 weeks it reaches 90% of the maximum, by 4 weeks it reaches its maximum and then remains constant. It is effective in adult patients with hypercholesterolemia with or without hypertriglyceridemia (regardless of race, gender, or age), including those with diabetes mellitus and familial hypercholesterolemia. In 80% of patients with hypercholesterolemia type IIa and IIb (Fredrickson classification) with an average baseline LDL cholesterol level of about 4.8 mmol / l, the LDL cholesterol concentration reaches values of less than 3 mmol/l when taking the drug at a dose of 10 mg. In patients with homozygous familial hypercholesterolemia, taking the drug at a dose of 20 mg and 40 mg, the average decrease in LDL cholesterol concentration is 22%.

The additive effect is observed in combination with fenofibrate (with respect to reducing the concentration of TG) and nicotinic acid in lipid-lowering doses > 1 g / day (with respect to increasing the concentration of HDL cholesterol).

Pharmacokinetics

Suction The maximum concentration (Cmax) of rosuvastatin in blood plasma is reached approximately 5 hours after taking the drug. Absolute bioavailability is approximately 20%. Systemic exposure to rosuvastatin increases in proportion to the dose. Pharmacokinetic parameters do not change with daily use.

Distribution Penetrates the placental barrier. Rosuvastatin is absorbed mainly by the liver, which is the main site of cholesterol synthesis and LDL-C metabolism. The volume of distribution is 134 liters. Binding to plasma proteins (mainly albumin) is approximately 90%.

Metabolism Biotransformed in the liver to a small extent (about 10%), being a non-core substrate for cytochrome P 450 isoenzymes. As with other HMG-CoA reductase inhibitors, a specific membrane transporter, an organic anion – transporting polypeptide (OATP), is involved in the hepatic uptake of the drug 1 In 1, which plays an important role in its hepatic elimination. The main isoenzyme involved in the metabolism of rosuvastatin is CYP2C9. The isoenzymes CYP2C19, CYP3A4, and CYP2D6 are less involved in metabolism. The main metabolites of rosuvastatin are N-desmethyl and lactone metabolites. N-desmethyl is approximately 50% less active than rosuvastatin, and the lactone metabolites are pharmacologically inactive. More than 90% of the pharmacological activity in inhibiting circulating HMG-CoA reductase is provided by rosuvastatin, the rest by its metabolites.

Deduction About 90% of the rosuvastatin dose is excreted unchanged through the intestines, and the remainder is excreted by the kidneys. The half-life (T1 / 2) is approximately 19 hours, does not change with increasing dose of the drug. The average plasma clearance is approximately 50 l / h (coefficient of variation 21.7%).

In patients with mild to moderate renal insufficiency, the plasma concentration of rosuvastatin or N-desmethyl does not change significantly. In patients with severe renal insufficiency (creatinine clearance < 30 ml / min), the plasma concentration of rosuvastatin is 3 times higher, and N-desmethyl is 9 times higher than in healthy volunteers. The plasma concentration of rosuvastatin in patients undergoing hemodialysis is approximately 50% higher than in healthy volunteers.

In patients with various stages of hepatic insufficiency with a Child-Pugh score of 7 or lower, there was no increase in rosuvastatin T1/2; in patients with Child-Pugh scores of 8 and 9, a 2-fold prolongation of T1/2 was observed. There is no experience of using the drug in patients with more severe hepatic impairment. Gender and age do not have a clinically significant effect on the pharmacokinetics of rosuvastatin. Pharmacokinetic parameters depend on race: the area under the concentration-time curve (AUC) in Japanese and Chinese is 2 times higher than that in residents of Europe and North America. In representatives of the Mongolian race and Indians, the average value of AUC and Cmax increases by 1.3 times.

Indications

• Primary hypercholesterolemia (type IIa according to Fredrickson), including heterozygous hereditary hypercholesterolemia) or mixed (combined) hyperlipidemia (type IIb according to Fredrickson), as an adjunct to diet and other non-drug measures (physical activity and weight loss);
• Homozygous form of hereditary hypercholesterolemia with insufficient effectiveness of diet therapy and other types of treatment aimed at reducing the level of lipids (for example, LDL apheresis) or if such types of treatment are not suitable for the patient.
• Hypertriglyceridemia (Fredrickson type IV) as a dietary supplement.
• To slow the progression of atherosclerosis as an adjunct to diet in patients who are indicated for therapy to reduce the concentration of total cholesterol and LDL cholesterol.
• Prevention of major cardiovascular complications (stroke, heart attack, arterial revascularization) in adult patients without clinical signs of coronary heart disease (CHD), but with an increased risk of its development (age over 50 years for men and over 60 years for women, increased concentration of C-reactive protein (≥ 2 mg / l) in the presence of at least one of the additional risk factors, such as arterial hypertension, low HDL cholesterol, smoking, family history of early

Use during pregnancy and lactation

Rozart is contraindicated during pregnancy and lactation.

The use of Rozart in women of reproductive age is possible only if reliable methods of contraception are used and if the patient is informed about the possible risk of treatment for the fetus.

Since cholesterol and substances synthesized from cholesterol are important for fetal development, the potential risk of HMG-CoA reductase inhibition exceeds the benefit of using the drug during pregnancy. If pregnancy is diagnosed during therapy with Rozart, the drug should be stopped immediately, and patients should be warned about the potential risk to the fetus.

There are no data on the excretion of rosuvastatin in breast milk, so if it is necessary to use the drug during lactation, taking into account the possibility of adverse events in infants, the question of stopping breastfeeding should be decided.

Contraindications

• liver disease in the active phase, including a persistent increase in serum liver transaminases (more than 3 times compared to the ULN) of unknown origin;
• pronounced renal dysfunction (CC less than 30 ml/min);
• myopathy;
• concomitant use of cyclosporine;
• women of reproductive age not using adequate contraception;
• pregnancy and lactation;
• age to 18 years (efficacy and safety not established);
• lactose intolerance, lactase deficiency, glucose-galactose malabsorption (product contains lactose monohydrate);
• hypersensitivity to rosuvastatin or other components of the drug;

With caution:  presence of risk factors for myopathy and/or rhabdomyolysis – renal failure (creatinine clearance greater than 30 ml/min), hypothyroidism, personal or family history of hereditary muscle diseases and a previous history of myotoxicity with other HMG-CoA reductase inhibitors or fibrates; excessive alcohol consumption, age over 70 years; conditions with increased plasma concentrations of rosuvastatin; race (Mongoloid race), concomitant use with fibrates, a history of liver disease, sepsis, hypotension, extensive surgery, trauma, severe metabolic, endocrine or electrolyte disorders, or uncontrolled epilepsy.

Side effects

From the central nervous system:  often – headache, dizziness, asthenic syndrome; infrequently-depression, anxiety, insomnia, paresthesia; very rarely-peripheral neuropathy, memory loss.

From the digestive system:  often – nausea, constipation, abdominal pain; infrequently-vomiting, diarrhea, flatulence; rarely-pancreatitis; very rarely-hepatitis, jaundice.

Respiratory system disorders: often – pharyngitis; infrequently-rhinitis, sinusitis, bronchial asthma, bronchitis, cough, dyspnoea, pneumonia.

From the cardiovascular system: infrequently – angina pectoris, increased blood pressure, palpitations, vasodilation.

From the endocrine system: common – diabetes mellitus 1. (The JUPITER study reported an overall incidence of 2.8% in the rosuvastatin group and 2.3% in the placebo group, mainly in patients with fasting glucose of 5.6-6.9 mmol/l. )

From the musculoskeletal system: often – myalgia; rarely-arthralgia; myopathy (including myositis), rhabdomyolysis, back pain, muscle hypertonus, pathological limb fracture; very rarely – immune-mediated necrotizing myopathy.

Allergic reactions: infrequently – skin pruritus, rash, urticaria; rarely-angioedema.

Skin and subcutaneous tissue: frequency unknown-Stevens-Johnson syndrome.

From the urinary system: often-proteinuria (mainly in patients receiving a dose of 40 mg), which decreases during therapy and is not associated with the occurrence of kidney disease, urinary tract infection; infrequently – peripheral edema, pain in the lower abdomen; very rarely – hematuria.

Laboratory parameters: infrequently-a transient dose-dependent increase in the activity of serum creatine phosphokinase (CPK), with an increase of more than 5 times compared to ULN, therapy should be temporarily suspended; rarely – a transient increase in the activity of aspartate aminotransferase and alanine aminotransferase.

Other services: often – back pain, rhinopharyngitis; rarely-decreased potency. As with other HMG-CoA reductase inhibitors, the frequency of occurrence is dose-dependent, and side effects are usually mild and resolve on their own.

Interaction

Concomitant use of rosuvastatin and cyclosporine does not affect the plasma concentration of cyclosporine, but the effect of rosuvastatin is enhanced (its excretion slows down, AUC increases by 7 times, Cmax – by 11 times).

Erythromycin enhances intestinal motility, which leads to a decrease in the effect of rosuvastatin (AUC decreases by 20% and Cmax by 30%).

In patients receiving vitamin K antagonists (such as warfarin), monitoring of MHO is recommended, since starting rosuvastatin therapy or increasing the dose of the drug may lead to an increase in MHO, and discontinuing rosuvastatin or reducing its dose may lead to a decrease in it.

Gemfibrozil enhances the effect of rosuvastatin (increases Cmax and AUC by 2 times). Simultaneous use of rosuvastatin and antacids containing aluminum and 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.

Concomitant use of rosuvastatin and oral contraceptives increases the AUC of ethinyl estradiol and AUC of norgestrel by 26% and 34%, respectively, which should be taken into account when selecting the dose of oral contraceptives. Pharmacokinetic data on the simultaneous use of rosuvastatin and hormone replacement therapy are not available, therefore, a similar effect cannot be excluded when using this combination.

The results of studies showed that rosuvastatin is neither an inhibitor nor an inducer of the action of cytochrome P450 isoenzymes. Rosuvastatin is a non-core substrate for these isoenzymes. There were no clinically significant interactions with drugs such as fluconazole, ketoconazole, and itraconazole associated with cytochrome P450 metabolism.

There is no clinically significant interaction of rosuvastatin with digoxin or fenofibrate. Gemfibrozil, other fibrates, and hypolipidemic doses of nicotinic acid (at least 1 g / day) increased the risk of myopathy when used concomitantly with other HMG-CoA reductase inhibitors. Possibly due to the fact that they can cause myopathy and when used as monotherapy.

Co-use of rosuvastatin and ezetimibe did not result in changes in the AUC or Cmax of either drug.

The use of protease inhibitors with rosuvastatin can lead to a pronounced increase in the effect of rosuvastatin. Therefore, co-use of rosuvastatin with protease inhibitors in HIV-infected patients is not recommended.

How to take, course of use and dosage

Inside, without chewing, without grinding, swallowing whole, washed down with water, regardless of the time of day and meal.

Before starting therapy with Rozart, the patient should start following a standard lipid-lowering diet and continue to follow it during treatment.

The dose of the drug should be selected individually, depending on the indications and therapeutic response, taking into account current generally accepted recommendations for target lipid concentrations. The recommended starting dose of Rozart for patients starting to take the drug, or for patients transferred from taking other HMG-CoA reductase inhibitors, is 5 or 10 mg 1 time per day. When choosing the initial dose, the patient’s cholesterol concentration should be guided and the risk of developing cardiovascular complications should be taken into account, as well as the potential risk of adverse reactions should be evaluated. If necessary, the dose of the drug can be increased after 4 weeks.

Due to the possible development of side effects when taking a dose of 40 mg compared to lower doses of the drug (see the section “Side effects”), final titration to a maximum dose of 40 mg should only be performed in patients with severe hypercholesterolemia and a high risk of cardiovascular complications (especially in patients with hereditary hypercholesterolemia), in whom the target cholesterol concentration was not reached when taking a dose of 20 mg, Especially careful monitoring of patients receiving the drug at a dose of 40 mg is recommended. After 2-4 weeks of therapy and/or an increase in the dose of the drug, monitoring of lipid metabolism parameters is necessary.

In elderly patients over 70 years of age, the recommended initial dose of Rozart is 5 mg, and no other dose adjustment is required.

In patients with hepatic insufficiency on the Child-Pugh scale below 7 points, no dose adjustment is required. In patients with Child-Pugh scores of 8 and 9, a preliminary assessment of renal function should be performed. There is no experience of using rosuvastatin in patients with hepatic insufficiency above 9 points on the Child-Pugh scale. Rosuvastatin is contraindicated in patients with active liver disease.

In patients with mild or moderate renal insufficiency, no dose adjustment is required. An initial dose of 5 mg is recommended for patients with moderate renal insufficiency (creatinine clearance less than 60 ml / min). In patients with moderate renal insufficiency (creatinine clearance less than 30-60 ml/min), the drug is contraindicated at a dose of 40 mg. Rozart is contraindicated in all doses in patients with severe renal insufficiency (creatinine clearance less than 30 ml / min).

Ethnic groups In patients of the Mongolian race, an increase in the systemic concentration of rosuvastatin is possible. The initial recommended dose of the drug for patients of the Mongolian race is 5 mg. The use of the drug in a dose of 40 mg is contraindicated in such patients.

Genetic polymorphism There are known types of genetic polymorphism that can lead to an increase in the systemic concentration of rosuvastatin. In patients with identified specific polymorphism, lower daily doses of rosuvastatin are recommended.

Patients predisposed to developing myopathy The initial recommended dose for these patients is 5 mg. The use of the drug in a dose of 40 mg in such patients is contraindicated.

Combination therapy Rosuvastatin is a substrate for various transport proteins (for example, OATP1 In 1 and BCRP). The risk of developing myopathy, including rhabdomyolysis, increases when rosuvastatin is co-administered with drugs that increase the concentration of rosuvastatin in blood plasma due to their interaction with transport proteins. This group of substances includes cyclosporine, HIV protease inhibitors, including the combination of ritonavir with atazanavir, lopinavir and / or tipranavir;

If possible, a decision should be made to prescribe alternative therapy and, if necessary, temporarily stop taking rosuvastatin. In cases where co-use cannot be avoided, the possible risk of interaction and the potential benefits of co-treatment should be carefully evaluated.

Overdose

With simultaneous use of several daily doses, the pharmacokinetic parameters of rosuvastatin do not change.

Treatment: There is no specific treatment, and symptomatic therapy is performed under the control of liver function and CKD activity. Hemodialysis is ineffective.

Special instructions

During treatment, especially during the period of dose adjustment of Rozart, the lipid profile should be monitored every 2-4 weeks and, if necessary, the dose of the drug should be changed accordingly.

It is recommended to determine liver function indicators before the start of therapy and 3 months after the start of therapy. Rozart should be discontinued or the dose of the drug should be reduced if the level of activity of “hepatic” transaminases in the blood serum is 3 times higher than the ULN.

When using the drug Rozart at a dose of 40 mg, it is recommended to monitor the indicators of renal function.

In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, treatment of the underlying diseases should be performed before starting treatment with Rozart. In patients with existing risk factors for rhabdomyolysis, it is necessary to consider the ratio of expected benefit and potential risk and conduct clinical monitoring throughout the course of treatment.

The patient should be informed of the need to immediately inform the doctor about cases of unexpected muscle pain, muscle weakness or spasms, especially in combination with malaise and fever. In such patients, the level of CPK should be determined. Therapy should be discontinued if the CPK level is significantly increased (more than 5 times the ULN) or if muscle symptoms are severe and cause daily discomfort. If symptoms disappear and CK levels return to normal, consideration should be given to re-prescribing Rozart or other HMG-CoA reductase inhibitors in smaller doses, with careful monitoring of the patient.

CPK determination should not be performed after intense physical activity or in the presence of other possible causes of increased CPK, which may lead to misinterpretation of the results obtained. If the initial CPK level is significantly elevated, a second measurement should be performed after 5-7 days – do not start therapy if the repeated test confirms the initial CPK level (5 times higher than normal).

Routine monitoring of CPK in the absence of symptoms is not advisable.

An increased incidence of myositis and myopathy has been reported in patients treated with other HMG-CoA reductase inhibitors in combination with fibrinic acid derivatives (including gemfibrozil), cyclosporine, nicotinic acid, azole antifungal drugs, protease inhibitors, and macrolide antibiotics. It is necessary to carefully weigh the ratio of expected benefit and potential risk when using Rozart and fibrates or niacin together, and the simultaneous use of gemfibrozil is not recommended.

In most cases, proteinuria decreases or disappears during therapy and does not mean the occurrence of acute or exacerbation of existing kidney disease. Evaluation of renal function should be carried out during routine examination of patients receiving a dose of 40 mg

. 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 exceeds the benefit of using the drug during pregnancy. If pregnancy occurs during therapy, the drug should be discontinued immediately. There are no data on the excretion of rosuvastatin in women’s milk, so breast-feeding should be discontinued.

Co-use of rosuvastatin and HIV protease inhibitors is not recommended.

Influence on the ability to drive vehicles and mechanisms

When driving vehicles and engaging in potentially dangerous activities, patients should be aware that dizziness may occur during therapy.

Composition

Tablet Form of production

Storage conditions

Does not require special storage conditions

Shelf life

30 months

Active ingredient

Rosuvastatin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets