Rosulip pills 20mg №28

pharmachologic effect

Rosulip - lipid-lowering.

Pharmacodynamics

Mechanism of action

Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase - an enzyme that catalyzes the conversion of 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonate, which is a precursor of cholesterol (Xc). Rosuvastatin increases the number of LDL receptors on the surface of liver cells, thereby enhancing the absorption and catabolism of LDL, and also suppresses the synthesis of VLDL in the liver. As a result, the total number of particles of VLDL and LDL is reduced.

Pharmacodynamic effects

It lowers the elevated concentration of low-density lipoprotein cholesterol (Xc-LDL), total cholesterol and triglycerides, and also increases the concentration of high-density lipoprotein cholesterol (Xc-HDL). In addition, rosuvastatin reduces the concentration of apolipoprotein B (ApoB), non-HDL cholesterol (Xc-non-LPVP), very low-density lipoprotein cholesterol (Xc-VLDL), very low-density lipoprotein triglycerides (TG-VLDL), and increases the content of apolipoprotein-low-density lipoprotein (TG-VLVP) and increases the content of apolipoprotein-very low density lipoprotein (TG-VLDL) and increases the content of apolipoprotein, low density lipoprotein, and low-density lipoprotein cholesterol and increases the content of apolipoprotein and low-density lipoprotein cholesterol; ). Also, rosuvastatin reduces the ratio of Xc-LDL / Xc-HDL, total cholesterol / Xc-HDL, Xc-non LPP / Xc-HDL and ApoV / ApoA-I.

The therapeutic effect of the drug is manifested within one week after the start of treatment. After 2 weeks of therapy, the efficiency reaches a level that is 90% of the maximum possible. The maximum therapeutic effect is usually achieved by the 4th week of therapy and is maintained with regular intake.

The safety and effectiveness of rosuvastatin in the pediatric population has not been proven. For this category of patients, the experience of using the drug is limited to a small number of patients (8 years old and older) with homozygous hereditary hypercholesterolemia.

Pharmacokinetics

Suction. C_max Rosuvastatin in plasma is reached approximately 5 hours after ingestion. The absolute bioavailability of the drug is about 20%.

Distribution. Rosuvastatin is intensively absorbed by the liver, where the main synthesis of cholesterol and the elimination of Xc-LDL occurs. V_d Rosuvastatin reaches 134 l.

Approximately 90% of rosuvastatin binds to plasma proteins, primarily albumin.

Metabolism. Rosuvastatin undergoes limited metabolism (about 10%) in the liver. It is a non-core substrate for cytochrome P450 isoenzymes. CYP2C9 is the main isoenzyme involved in rosuvastatin metabolism. The isozymes CYP2C19, CYP3A4 and CYP2D6 are less involved in metabolism. The main identified metabolites of rosuvastatin are N-desmethylrozuvastatin and lactone metabolites. N-desmethylrosuvastatin is approximately 50% less active than rosuvastatin, lactone metabolites are pharmacologically inactive. More than 90% of the pharmacological activity on inhibition of circulating HMG-CoA reductase is provided by rosuvastatin, the rest is provided by its metabolites.

Inference. Approximately 90% of the dose of rosuvastatin is excreted unchanged through the intestines.

Approximately 5% of the dose is excreted by the kidneys unchanged. T_1/2 drug from blood plasma is approximately 19 hours and does not change with increasing dose of the drug. Rosuvastatin plasma clearance reaches an average of 50 l / h (coefficient of variation - 21.7%).

As in the case of other HMG-CoA reductase inhibitors, a membrane cholesterol transporter is involved in the process of hepatic uptake of rosuvastatin, which plays an important role in the hepatic elimination of rosuvastatin.

The systemic bioavailability of rosuvastatin increases in proportion to the dose. When using the drug several times a day, pharmacokinetic parameters do not change.

Special patient groups

Gender and age do not have a clinically significant effect on rosuvastatin pharmacokinetics.

Pharmacokinetic studies have shown an approximately two-fold increase in median AUC and C_max Rosuvastatin in the blood plasma of patients of the Asian race (Japanese, Chinese, Filipinos, Vietnamese and Koreans), compared with Caucasians; Indian patients showed an increase in median AUC and C_max 1.3 times. The analysis did not reveal clinically significant differences in pharmacokinetics among Europeans and representatives of the Negroid race.

In patients with mild and moderate renal insufficiency, the plasma concentration of rosuvastatin or N-desmethylrozuvastatin does not change significantly.

In patients with severe renal insufficiency (Cl creatinine less than 30 ml / min), plasma concentration of rosuvastatin is 3 times higher, and N-desmethylrozuvastatin concentration is 9 times higher than in healthy volunteers. The plasma concentration of rosuvastatin in hemodialysis patients was about 50% higher than in healthy volunteers.

No increase in T was found in patients with different stages of liver failure._1/2Rosuvastatin (patients with a score of 7 or lower on the Child-Pugh scale). 2 patients with grades 8 and 9 on the Child-Pugh scale showed an increase in T_1/2at least 2 times. Experience with rosuvastatin in patients with a score above 9 on the Child-Pugh scale is absent.

Indications

• primary hypercholesterolemia (type IIa according to Fredrickson) or mixed hypercholesterolemia (type IIb), as a supplement to the diet, when diet and other non-pharmacological treatment methods (eg exercise, weight loss) are insufficient;
• homozygous hereditary hypercholesterolemia, as a supplement to the diet and other methods of treatment aimed at reducing the level of lipids in the blood (such as LDL apheresis), as well as in cases when these methods are not sufficiently effective;
• hypertriglyceridemia (type IV by Fredrickson), as a supplement to the diet;
• to slow the progression of atherosclerosis, as a supplement to the diet in patients, including which shows therapy to reduce the level of total Xc and Xc-LDL;
• 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 (age over 50 years - for men and over 60 years - for women, increased concentration C -reactive protein (≥2 mg / l) in the presence of at least one of the additional risk factors such as hypertension, low concentration of HDL-C, smoking, a family history of early onset ischemic pain heart ailments.

Contraindications

• hypersensitivity to rosuvastatin and other components of the drug Rosulip;
• liver diseases in the active phase, including a persistent increase in serum transaminase activity or an increase in serum transaminase activity by more than 3 times as compared with VGN;
• severe renal impairment (Cl creatinine less than 30 ml / min);
• myopathy;
• simultaneous administration of cyclosporine;
• pregnancy, lactation, and the lack of adequate methods of contraception in women with intact reproductive function;
• predisposition to the development of myotoxic complications;
• children up to 18 years of age (due to the lack of sufficient clinical data, efficacy and safety have not been established);
• lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the product contains lactose).

Carefully: risk of myopathy / rhabdomyolysis - renal failure, hypothyroidism, personal or family history of hereditary muscular diseases and a previous history of muscle toxicity when using other HMG-CoA reductase inhibitors or fibrates; excessive drinking; patients over 65; conditions in which there is an increase in the plasma concentration of rosuvastatin; Asian patients; simultaneous use with fibrates; history of liver disease; sepsis; hypotension; extensive surgery, trauma; severe metabolic, endocrine or electrolyte disturbances, or uncontrolled seizures.

Use during pregnancy and lactation

Rosulip is contraindicated during pregnancy and lactation (breastfeeding). When diagnosing pregnancy during therapy, the drug should be discontinued immediately.

Women of reproductive age should use adequate methods of contraception. Since Xc and its biosynthesis products are important for the development of the fetus, the potential risk of inhibition of HMG-CoA reductase exceeds the benefits of the drug.

Data on the allocation of rosuvastatin with breast milk are not available, so if you need to use the drug during lactation, breastfeeding should be stopped.

special instructions

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

When using the drug Rosulip in all doses, especially more than 20 mg, it was reported about the development of myalgia, myopathy and in rare cases of rhabdomyolysis.

Determination of CPK activity should not be carried out after intense physical exertion or in the presence of other possible reasons for an increase in CPK activity, which may lead to a misinterpretation of the results obtained. If the initial activity of CPK is significantly increased (5 times higher than VGN), after 5-7 days it is necessary to re-measure. It is not necessary to begin therapy if the repeated test confirms the increased activity of KFK (5 times higher than VGN).

When prescribing Rosulip (as well as other HMG-CoA reductase inhibitors) in patients with existing risk factors for rhabdomyolysis, it is necessary to consider the ratio of the expected benefit and potential risk and conduct clinical observation.

The patient should be informed of the need to immediately report to the doctor about cases of sudden onset of muscle pain, muscle weakness or spasms, especially in combination with indisposition and fever. In such patients, the activity of CPK should be determined. Therapy should be discontinued if the activity of CPK is significantly increased (more than 5 times compared to VGN) or if the muscular symptoms are pronounced and cause daily discomfort (even if the activity of KFK is 5 times less than VGN). If the symptoms disappear and the activity of CPK returns to normal, consideration should be given to reappointment of Rosulip or other HMG-CoA reductase inhibitors in smaller doses with careful monitoring of the patient.

Routine monitoring of CPK activity in the absence of symptoms is impractical.

There are no signs of an increase in toxic effects on skeletal muscles when using Rosulip as part of a combination therapy. An increase in the incidence of myositis and myopathy was reported in patients taking other HMG-CoA reductase inhibitors in combination with fibric acid derivatives (including gemfibrozil), cyclosporine, nicotinic acid in lipid-lowering doses (more than 1 g / day), azole antifungal agents, inhibitors proteases and macrolide antibiotics. Gemfibrozil increases the risk of myopathy, while the appointment with some HMG-CoA reductase inhibitors. Thus, simultaneous administration of Rosulip and gemfibrozil is not recommended. It is necessary to carefully weigh the ratio of the expected benefit and potential risk in the combined use of Rosulip and fibrates or nicotinic acid in lipid-lowering doses (more than 1 g / day).

After 2-4 weeks after the start of treatment and / or with increasing doses of the drug Rosulip, monitoring of lipid metabolism indices is necessary (if necessary, dose adjustment is required).

It is recommended to determine the activity of transaminases before the start of therapy and 3 months after the start of therapy.Taking Rosulip should stop or reduce the dose of the drug if the activity of transaminases in the serum is 3 times higher than VGN.

In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, treatment of major diseases should be carried out before starting treatment with Rosulip.

Clinical experience and data on the use of the drug in patients with impaired liver function in excess of 9 points on the Child-Pugh scale are not available.

Very rare cases of interstitial lung disease were recorded in patients who received certain drugs from the group of statins. As a rule, these cases were observed with long-term statin therapy. Interstitial lung disease is manifested by shortness of breath, an unproductive cough and deterioration of the general condition (fatigue, weight loss and fever). If interstitial lung disease is suspected, statin therapy should be discontinued.

The results of pharmacokinetic studies indicate that in patients of the Asian race, the bioavailability of rosuvastatin is higher than in Europeans.

This drug should not be taken by patients with lactose intolerance, lactase deficiency or glucose-galactose malabsorption, since The drug contains lactose.

Use in pediatrics

The efficacy and safety of the drug in children under 18 years of age has not been established. The experience of using the drug in pediatric practice is limited to a small number of children (8 years old and older) with familial homozygous hypercholesterolemia. Currently, it is not recommended to use Rosulip in children.

Influence on the ability to drive a car or perform work that requires increased speed of physical and mental reactions. Patients should be careful when driving and work that requires increased concentration and psychomotor speed, because dizziness may occur during therapy.

Composition

1 tablet contains:

Active substance: Rosuvastatin Zinc;

Excipients: ludipress; Povidone; crospovidone; crospovidone; Magnesium stearate;

Shell film: Opadry II White 85F 18422; titanium dioxide; macrogol 3350; talc.

Dosage and administration

Inside Do not chew or crush the pill, swallow it whole with water.Rosulip can be taken at any time of the day, regardless of the meal.

Before starting treatment with Rosulip, the patient should be prescribed a standard diet low in cholesterol. The patient must follow a diet during the entire course of therapy. The dose of the drug should be selected individually depending on the indications and therapeutic response to treatment, taking into account the current recommendations on target lipid levels.

The recommended initial dose of Rosulip for patients starting the drug or transferred from receiving other HMG-CoA reductase inhibitors is 5 or 10 mg once a day. When choosing the initial dose, one should be guided by the patient’s cholesterol content and take into account the risk of cardiovascular complications, and the potential risk of side effects should be assessed. If necessary, after 4 weeks the dose may be increased.

After taking a dose for 4 weeks that exceeds the recommended initial dose, its subsequent increase to 40 mg can be performed only in patients with severe hypercholesterolemia and a high risk of cardiovascular complications (especially in patients with familial hypercholesterolemia) who have not achieved the desired result therapy when receiving a dose of 20 mg and which will be under the supervision of a specialist. Especially careful monitoring of patients receiving the drug at a dose of 40 mg is recommended.

For treatment of patients over 65, the recommended starting dose is 5 mg. There is no need for other changes in the dose of the drug related to the age of the patients.

Patients with renal insufficiency of mild or moderate severity dose adjustment is not required. Patients with moderate renal impairment (creatinine Cl less than 60 ml / min) are recommended an initial dose of 5 mg. A dose of 40 mg is contraindicated in patients with moderate renal impairment. In severe renal failure, Rosulip is contraindicated in any doses.

When prescribing doses of 10 and 20 mg, the recommended starting dose for patients of the Asian race is 5 mg. The drug is contraindicated in a dose of 40 mg for patients of the Asian race.

When prescribing doses of 10 and 20 mg, the recommended initial dose for patients predisposed to myopathy is 5 mg. The drug is contraindicated in d