SUVARDIO PILLS 10MG

Trade name of the drug: Suvardio®.
International non-proprietary name: Rosuvastatin.
Dosage Form: film coated tablets

Active ingredient

1 pill 5 mg contains: active substance: rosuvastatin Calcium in terms of rosuvastatin - 5,000 mg; Excipients: anhydrous lactose - 58,690 mg; silicon dioxide colloidal anhydrous - 0,330 mg; microcrystalline cellulose, silicatized - 27,500 mg; dry corn starch - 16,500 mg; talc - 1,100 mg; sodium fumarate - 0.880 mg;tablet shell: hypromellose-2910 - 1,860 mg; mannitol - 0.150 mg; macrogol 6000 - 0.090 mg; titanium dioxide - 0.645 mg; iron (III) oxide, yellow - 0.056 mg; iron (III) oxide, red - 0,019 mg; talc - 0.180 mg; talc (polishing agent)2 - 0.057 mg.

1 pill 10 mg contains: active substance: rosuvastatin calcium in terms of rosuvastatin - 10,000 mg; Excipients: anhydrous lactose - 53,690 mg; silicon dioxide colloidal anhydrous - 0,330 mg; microcrystalline cellulose, silicatized - 27,500 mg; dry corn starch - 16,500 mg; talc - 1,100 mg; sodium fumarate - 0.880 mg;tablet shell: hypromellose-2910 - 1,860 mg; mannitol - 0.150 mg; macrogol 6000 - 0.090 mg; titanium dioxide - 0.420 mg; iron (III) oxide, yellow - 0.225 mg; iron (III) oxide, red - 0.075 mg; talc - 0.180 mg; talc (polishing agent)2 - 0.057 mg.

1 pill 20 mg contains: active substance: rosuvastatin calcium in terms of rosuvastatin - 20,000 mg; Excipients: anhydrous lactose - 107.380 mg; colloidal anhydrous silicon dioxide - 0.660 mg; microcrystalline cellulose, silicatized - 55,000 mg; dry corn starch - 33,000 mg; talc - 2,200 mg; sodium fumarate - 1,760 mg;tablet shell: hypromellose-2910 - 3.720 mg; mannitol - 0,300 mg; macrogol 6000 - 0.180 mg; titanium dioxide - 0.840 mg; iron (III) oxide, yellow - 0,450 mg; iron (III) oxide, red - 0.150 mg; talc - 0.360 mg; talc (polishing agent)2 - 0.113 mg.

1 pill 40 mg contains: active substance: rosuvastatin calcium in terms of rosuvastatin - 40,000 mg; Excipients: anhydrous lactose - 214.760 mg; silicon dioxide colloidal anhydrous - 1,320 mg; microcrystalline cellulose, silicatized - 110,000 mg; dry corn starch - 66,000 mg; talc - 4,400 mg; sodium fumarate - 3,520 mg;tablet shell: hypromellose-2910 - 7,440 mg; mannitol - 0.600 mg; macrogol 6000 - 0.360 mg; titanium dioxide - 1,680 mg; iron (III) oxide, yellow - 0.900 mg; iron (III) oxide, red - 0,300 mg; talc - 0.720 mg; talc (polishing agent)2 - 0,226 mg.

2 - used for polishing the tablet, the total amount is not included.

Pharmacodynamics

Rosuvastatin is a selective, competitive inhibitor of HMG-CoA reductase - an enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A into mevalonate, the precursor of cholesterol. Rosuvastatin acts on the liver, where cholesterol (cholesterol) and low density lipoprotein catabolism are being synthesized.

Rosuvastatin increases the number of LDL receptors on the surface of hepatocytes, which enhance the uptake and catabolism of LDL, and inhibits the synthesis of very low density lipoproteins (VLDL) by the liver,thereby reducing the amount of LDL and VLDL.

Rosuvastatin reduces the concentration of low-density cholesterol-lipoproteins (LDL-C), total cholesterol, triglycerides (TG), increases the concentration of high-density lipoprotein-cholesterol (HDL-C), and also decreases the concentration of apolipoprotein B (ApoV), LDL-HDLP, - VLDL, TG-VLDL and increases the concentration of apolipoprotein A-1 (ApoA-1) (see Table 1), reduces the ratio of XC-LDL / XC-HDL, total XC / XC-HDL and XC-non-IDP / XC-LDL and ApoB / ApoA-1 ratio.

After initiation of rosuvastatin therapy, the therapeutic effect appears within one week, after 2 weeks of treatment it reaches 90% of the maximum possible effect. The maximum therapeutic effect is usually achieved by week 4 and is maintained with regular use of the drug.

Table 1.The dependence of the response to treatment on the dose of rosuvastatin in patients with primary hypercholesterolemia (types IIa and IIb according to Fredrickson)
(average adjusted percentage change from baseline)

Clinical efficacy

Rosuvastatin is effective in adult patients with hypercholesterolemia, with or without hypertriglyceridemia, regardless of race, gender, or age, including patients with diabetes and familial hypercholesterolemia.

In 80% of patients with hypercholesterolemia IIa and IIb type according to Fredrickson's classification (the average initial concentration of LDL-C is about 4.8 mmol / l) when using rosuvastatin at a dose of 10 mg, the concentration of LDL-C makes up less than 3 mmol / l.

Patients with heterozygous familial hypercholesterolemia who took rosuvastatin in doses of 20 to 80 mg according to the forced dose titration scheme showed a positive trend in lipid profile parameters. After the titration of the daily dose to 40 mg per day (12 weeks of therapy), the concentration of LDL-C decreased by 53%. In 33% of patients, a decrease in LDL-C concentration of less than 3 mmol / L was achieved.

In patients with homozygous familial hypercholesterolemia who took rosuvastatin at doses of 20 and 40 mg, the average decrease in LDL-C concentration was 22%.

The additive effect is observed in combination with fenofibrate in relation to the concentration of TH and with nicotinic acid (more than 1 g per day) in relation to the concentration of HDL-C.

In patients with a low risk of developing coronary heart disease (CHD) (Framingham risk less than 10% over a period of more than 10 years), with an average concentration of LDL-C of 4.0 mmol / L (154.5 mg / dL) and subclinical atherosclerosis estimated by the thickness of the intima-media complex of the carotid arteries (TCIM), rosuvastatin at a dose of 40 mg / day significantly slowed the rate of progression of the maximum TCIM for 12 segments of the carotid artery compared with placebo at a rate of 0.0145 mm / year (95% confidence interval (CI): from -0.0,0196 to -0.0093, with p <0.0001). The dose of 40 mg should be prescribed only to patients with severe hypercholesterolemia and a high risk of developing cardiovascular diseases.

Pharmacokinetics

Absorption

Maximum concentration (Cmaxa) Rosuvastatin in plasma is reached approximately 5 hours after ingestion. Absolute bioavailability is ≈ 20%.

Distribution

Rosuvastatin is metabolized mainly by the liver, which is the main site of cholesterol synthesis and metabolism of LDL-C. The volume of distribution of rosuvastatin is approximately 134 liters. About 90% of rosuvastatin binds to plasma proteins , mainly albumin.

Metabolism

A limited amount of rosuvastatin (approximately 10%) is subject to biotransformation.

Rosuvastatin metabolism is slightly associated with cytochrome P450 isoenzymes. CYP2C9 isoenzyme is the main isoenzyme involved in rosuvastatin metabolism, while CYP2C19, CYP3A4 and CYP2D6 isoenzymes are less involved in metabolism.

The main identified metabolites of rosuvastatin are N-dismethylrozuvastatin 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.

Removal

Approximately 90% of the received dose of rosuvastatin is excreted unchanged through the intestine (including absorbed and unabsorbed rosuvastatin), the rest is excreted by the kidneys. Unchanged by the kidneys excreted about 5% of the administered dose of the drug.The half-life (T1/2) is 19 hours, does not change with increasing dose of the drug. The geometric mean plasma clearance is approximately 50 l / h (coefficient of variation 21.7%). As in the case of other HMG-CoA reductase inhibitors, membrane cholesterol transporter is involved in the hepatic capture process of rosuvastatin. This carrier plays a major role in the removal of rosuvastatin by the liver.

Linearity

Systemic exposure of rosuvastatin increases in proportion to the dose. After repeated daily administration of the drug, no change in pharmacokinetic parameters occurs.

Genetic polymorphism

The HMC-CoA reductase inhibitors, including rosuvastatin, bind to the OATP1B1 transport proteins (a polypeptide of organic anion transport that participates in the capture of statins by the hepatocytes) and HRRP (efflux transporter). In carriers of the SLCO1B1 (OATP1B1) C.521CC and ABCG2 (BCRP) C.421AA genotypes, there was an increase in exposure (AUC - area under the concentration-time curve) of rosuvastatin 1.6 and 2.4 times, respectively, compared to carriers genotypes SLCO1B1c.521TT and ABCG2 c.421AA.

Special patient populations

Age and gender

Age and gender do not have a clinically significant effect on the pharmacokinetic parameters of rosuvastatin.

Ethnic groups

Pharmacological studies have shown approximately a twofold increase in the median AUC and Cmax Rosuvastatin in patients of the Mongoloid race (Japanese, Chinese, Filipinos, Vietnamese and Koreans) compared with those of Caucasians; Hindu patients showed an increase in median AUC and Cmax about 1.3 times. At the same time, the analysis of pharmacokinetics indicators for the entire studied population did not reveal clinically significant differences in the pharmacokinetics of the drug among representatives of the Caucasian and Negroid races.

Renal failure

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

Liver failure

patients with varying degrees of liver failure with a score of 7 and below on the Child-Pugh scale did not reveal an increase in T1/2 Rosuvastatin. However, 2 patients with grades 8 and 9 on the Child-Pugh scale showed an elongation of T1/2, approximately 2 times higher than the same indicator for patients with lower rates on the Child-Pugh scale. Experience with rosuvastatin in patients with a score above 9 on the Child-Pugh scale is absent.

• primary hypercholesterolemia according to Fredrickson's classification (type IIa, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb) as a supplement to the diet when diet and other non-drug therapies are insufficient;
• familial homozygous hypercholesterolemia as an adjunct to diet and other lipid-lowering therapy (for example, LDL-apheresis), or in cases when such therapy is not sufficiently effective;
• hypertriglyceridemia (Fredrickson type IV) as a supplement to the diet;
• to slow down