Suvardio pills 20mg, 28pcs

Composition

1 tablet of 20 mg contains:

Active ingredient:  

rosuvastatin calcium in terms of rosuvastatin-20,000 mg;

excipients:

anhydrous lactose-107.380 mg;

colloidal anhydrous silicon dioxide-0.660 mg;

microcrystalline cellulose,

silicated – 55,000 mg;

dry corn starch-33,000 mg;

talc – 2,200 mg;

sodium stearyl 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

Pharmacological action

Pharmacotherapy group:

hypolipidemic agent-HMG-CoA reductase inhibitor.

ATX code: C10AA07.

Pharmacological properties

Pharmacodynamics

Rosuvastatin is a selective, competitive inhibitor of HMG-CoA reductase, an enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a cholesterol precursor. Rosuvastatin acts on the liver, where the synthesis of cholesterol (cholesterol) and catabolism of low-density lipoproteins (LDL) is carried out.

Rosuvastatin increases the number of LDL receptors on the surface of hepatocytes, which increase 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 lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides (TG), increases the concentration of high-density lipoprotein cholesterol (HDL-C), and also reduces the concentration of apolipoprotein B (apoB), HDL-C, VLDL-C, VLDL-C and increases the concentration of apolipoprotein A-1 (ApoA-1) (see Table 1), reduces the LDL-C/HDL-C ratio, total cholesterol/HDL-C and non-HDL-C/HDL-C ratio, and the apoB/ApoA-1 ratio.

After starting therapy with rosuvastatin, 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 4 weeks and is maintained with regular use of the drug.

Clinical efficacy

Rosuvastatin 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 Fredrickson’s type IIa and type IIb hypercholesterolemia (mean baseline LDL-C concentration of about 4.8 mmol / L), the LDL-C concentration reaches less than 3 mmol/L when rosuvastatin is administered at a dose of 10 mg. In patients with heterozygous familial hypercholesterolemia who took rosuvastatin in doses from 20 to 80 mg according to the scheme of forced titration of doses, there was a positive dynamics of lipid profile indicators. After titration of the daily dose to 40 mg per day (12 weeks of therapy), the LDL-C concentration 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 received 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 TG 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 scale risk of less than 10% over a period of more than 10 years), with an average LDL-C concentration of 4.0 mmol/L (154.5 mg/dl) and subclinical atherosclerosis, which was assessed by the thickness of the intima-media complex of the carotid arteries (IMT), rosuvastatin at a dose of 40 mg/day significantly slowed the rate of progression of maximum IMT for 12 segments carotid artery disease compared to placebo at a rate of -0.0145 mm/yr (95% confidence interval (CI): -0.0196 to-0.0093, at p The 40 mg dose should only be given to patients with severe hypercholesterolemia and a high risk of developing cardiovascular diseases.

Pharmacokinetics

Absorption rate The maximum concentration (Cmax) of rosuvastatin in blood plasma is reached approximately 5 hours after oral use. The absolute bioavailability is ≈ 20%.

Distribution Rosuvastatin is primarily metabolized by the liver, which is the main site of cholesterol synthesis and LDL-C metabolism. 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 biotransformed. Rosuvastatin metabolism is only slightly associated with cytochrome P450 isoenzymes. CYP2C9 is the main isoenzyme involved in rosuvastatin metabolism, while CYP2C19, CYP3A4, and CYP2D6 are less involved in the metabolism.

The main identified metabolites of rosuvastatin are N-dismethylrosuvastatin and lactone metabolites.

N-desmethylrosuvastatin 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 Approximately 90% of the administered rosuvastatin dose is excreted unchanged through the intestine (including absorbed and unabsorbed rosuvastatin), the remainder is excreted by the kidneys. Approximately 5% of the administered dose is excreted unchanged by the kidneys. The half-life (T 1/2) is 19 hours, does not change with increasing dose of the drug. The average geometric plasma clearance is approximately 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. This transporter plays an important role in the elimination of rosuvastatin by the liver.

Linearity Systemic exposure to rosuvastatin increases in proportion to the dose. After repeated daily use of the drug, no changes in pharmacokinetic parameters occur.

Genetic polymorphism HMC-CoA reductase inhibitors, including rosuvastatin, bind to the transport proteins OATP 1 In 1 (an organic anion transport polypeptide involved in statin uptake by hepatocytes) and BCRP (efflux transporter). Carriers of the SLCO1B1 (OATR 1V1) C. 521CC and ABCG2 (BCRP) C. 421AA genotypes showed a 1.6 – and 2.4 – fold increase in rosuvastatin exposure (AUC-area under the concentration-time curve), respectively, compared to carriers of the SLCO1B1c. 521TT and ABCG2 c. 421AA genotypes.

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 an approximately twofold increase in the median AUC and Cmax of rosuvastatin in patients of the Mongolian race (Japanese, Chinese, Filipino, Vietnamese, and Korean) compared with those of the Caucasian race; in Indian patients, an increase in the median AUC and Cmax is approximately 1.3 times. At the same time, the analysis of pharmacokinetic parameters for the entire study population did not reveal clinically significant differences in the pharmacokinetics of the drug among representatives of the Caucasian and Black races.

Kidney failure In patients with mild to moderate renal insufficiency, the plasma concentration of rosuvastatin or N-desmethylrosuvastatin does not change significantly. In patients with severe renal insufficiency (creatinine clearance < 30 ml / min), the concentration of rosuvastatin in blood plasma is 3 times higher, and the concentration of N-desmethylrosuvastatin 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.

Liver failure No increase in rosuvastatin T 1/2 was detected in patients with varying degrees of hepatic insufficiency with a Child-Pugh score of 7 or lower. However, in 2 patients with Child-Pugh scores of 8 and 9, an elongation of T 1/2 was observed, approximately 2 times higher than the same indicator for patients with lower Child-Pugh scores. There is no experience of using rosuvastatin in patients with a score higher than 9 on the Child-Pugh scale.

Indications

• Fredrickson’s primary hypercholesterolemia (type IIa, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb) as an adjunct to diet when diet and other non-drug treatments are insufficient; • familial homozygous hypercholesterolemia as an adjunct to diet and other lipid-lowering therapy (for example, LDL apheresis), or in cases where such therapy is not sufficient effective; • 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 concentration of total cholesterol and LDL-C. • primary prevention of major cardiovascular complications (stroke, heart attack, unstable angina, 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 in men, over 60 years in women, increased concentration of C-reactive protein (≥ 2 mg/l) in the presence of at least one additional risk factor, such as arterial hypertension, low HDL-C concentration, smoking, family history of early-onset CHD).

Contraindications

* hypersensitivity to rosuvastatin or any of the components of the drug; • liver diseases in the active phase, including a persistent increase in the activity of “hepatic” transaminases, as well as any increase in the activity of” hepatic ” transaminases in blood serum by more than 3 times compared to the upper limit of normal (ULN) • * severe renal dysfunction (creatinine clearance less than 30 ml / min); • myopathy; • concomitant use of cyclosporine • * pregnancy, breast-feeding; • use in patients predisposed to the development of myotoxic complications • * lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome (the drug contains lactose); • age up to 18 years (efficacy and safety have not been established).

With caution

For a daily dose of 5 mg,10 mg and 20 mg: risk of developing myopathy/rhabdomyolysis – renal failure, hypothyroidism; personal or family history of inherited muscle diseases and previous history of muscle toxicity with other HMG-CoA reductase inhibitors (statins) or fibrates; excessive alcohol consumption; conditions with increased plasma concentrations of rosuvastatin; age over 65 years; high risk of diabetes mellitus; a history of liver disease; sepsis; arterial hypertension hypotension; extensive surgical interventions; injuries; severe metabolic, endocrine or water-electrolyte disorders; uncontrolled epilepsy; race (Mongoloid race); simultaneous intake of fibrates.

Side effects

According to the World Health Organization (WHO), adverse reactions are classified according to their frequency as follows: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000) and very rare (

Disorders of the blood and lymphatic system frequency unknown: thrombocytopenia.

Immune system disorders are rare: hypersensitivity reactions, including angioedema.

Disorders of the endocrine system are common: type 2 diabetes mellitus.

Central nervous system disorders are common: headache, dizziness; very rarely: polyneuropathy, memory loss.

Respiratory system disorders frequency unknown: cough, shortness of breath.

Disorders of the digestive system are common: constipation, nausea, abdominal pain; rarely: pancreatitis; frequency unknown: diarrhea.

Skin disorders infrequently: skin pruritus, rash, urticaria; frequency unknown: Stevens-Johnson syndrome.

Laboratory parameters Increased creatine phosphokinase (CPK) activity, glucose concentration, glycosylated hemoglobin, bilirubin in blood plasma, gamma-glutamyltranspeptidase activity, alkaline phosphatase, thyroid dysfunction.

Other frequently: asthenic syndrome, gynecomastia, peripheral edema.

Urinary system disorders are very rare: hematuria.

When taking rosuvastatin, proteinuria may occur. Changes in the protein content in the urine (from the absence to the presence of trace amounts to ++ and higher) are observed in less than 1% of patients taking rosuvastatin at a dose of 10 mg and 20 mg, and in approximately 3% taking the drug at a dose of 40 mg.

A slight change in the amount of protein in the urine, expressed in a change from zero or traces to+, was observed when taking the drug at a dose of 20 mg. In most cases, proteinuria decreased and passed independently during treatment. No causal association between proteinuria and acute or progressive kidney disease was found in the analysis of clinical trials.

Musculoskeletal and connective tissue disorders are common: myalgia; rarely: myopathy (including myositis), rhabdomyolysis; very rarely: arthralgia; frequency unknown: immune-mediated necrotizing myopathy.

Liver and biliary tract disorders are rare: increased activity of “hepatic” transaminases; very rarely: jaundice, hepatitis.

Adverse events such as depression, sleep disorders including insomnia and nightmares, and sexual dysfunction have been reported with some statins.

Interaction

When rosuvastatin and cyclosporine were co-administered, the AUC of rosuvastatin was on average 7 times higher than that observed in healthy volunteers. The combined use of these drugs leads to an 11-fold increase in the concentration of rosuvastatin in blood plasma, while the plasma concentration of cyclosporine does not change (see the section “Contraindications”).

When using other statins, cases of rhabdomyolysis have been reported with the simultaneous use of rosuvastatin and fusidic acid, monitoring of the patient’s condition is necessary, and if necessary, temporary discontinuation of rosuvastatin is possible.

As with other HMG-CoA reductase inhibitors, starting rosuvastatin therapy or increasing the dose of the drug in patients receiving concomitant vitamin K antagonists (for example, warfarin or other coumarin anticoagulants) may lead to an increase in the international normalized ratio (MHO). Discontinuation or reduction of the rosuvastatin dose may cause a decrease in MHO. In such cases, the MHO should be monitored.

Concomitant use of rosuvastatin and gemfibrozil and other agents that reduce the concentration of lipids leads to a 2-fold increase in the Cmax and AUC of rosuvastatin.

How to take, course of use and dosage

Inside. At any time of the day, regardless of the meal. The tablet should not be chewed, crushed, swallowed whole, washed down with water.

Before starting Suvardio therapy, the patient should begin to follow a standard hypocholesterolemic diet and continue to follow it throughout the entire period of therapy.

The dose of Suvardio® is selected individually, taking into account the target indicators of cholesterol concentration and individual therapeutic response to the therapy.

Recommended starting dose of Suvardio® It is 5 mg or 10 mg once a day for both patients who have not previously taken statins, and for patients transferred to taking this drug after therapy with other HMG-CoA reductase inhibitors. When choosing the initial dose, the concentration of cholesterol and the possible risk of cardiovascular complications in this patient should be considered, and the potential risk of side effects should be evaluated. If necessary, after 4 weeks, you can adjust the dose of the drug.

Due to the possible development of side effects when taking a dose of 40 mg compared to lower doses of the drug, 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), who did not reach the target cholesterol concentration when taking a dose of 20 mg, and who will When prescribing a dose of 40 mg, careful medical supervision is recommended.

It is not recommended to prescribe a dose of 40 mg to patients who have not previously consulted a doctor.

Elderly patients For patients over 65 years of age, the recommended starting dose is Suvardio® it is 5 mg. In all other cases, dose adjustment due to age is not required.

Patients with renal insufficiency In patients with mild or moderate renal insufficiency, adjust the dose of Suvardio® not required. The recommended starting dose of the drug is 5 mg for patients with moderate renal insufficiency (creatinine clearance less than 60 ml / min). The use of Suvardio® in any dose is contraindicated in patients with severe renal insufficiency (creatinine clearance less than 30 ml / min).section “Contraindications”).

Patients with moderate renal insufficiency should not be prescribed the drug at a dose of 40 mg (see the section “Contraindications”).

Patients with hepatic insufficiency There was no increase in the systemic concentration of rosuvastatin in patients with a Child-Pugh score of 7 or lower. However, an increase in the systemic concentration of rosuvastatin was observed in patients with Child-Pugh scores of 8 and 9. In such patients, liver function should be monitored during rosuvastatin therapy. There are no data on the use of rosuvastatin in patients with a Child-Pugh score higher than 9. Rosuvastatin is contraindicated in patients with active liver disease (see section “Contraindications”).

Special populationsEthnic groups In patients of the Mongolian race, an increase in the systemic concentration of rosuvastatin in blood plasma is possible. Recommended starting dose of Suvardio® in patients of the Mongolian race is 5 mg. The use of the drug in a dose of 40 mg is contraindicated in such patients (see the section “Contraindications”).

Patients predisposed to develop myopathy The recommended starting dose of Suvardio® for patients predisposed to develop myopathy is 5 mg. The use of the drug in a dose of 40 mg is contraindicated in such patients (see the section “Contraindications”).

Genetic polymorphism Carriers of the SLCO1B1 (OATP 1V1) C. 521CC and ABCG2 (BCRP) C. 421AA genotypes showed a 1.6-and 2.4-fold increase in rosuvastatin exposure (AUC), respectively, compared to carriers of the SLCO1B1c. 521TT and ABCG2 c. 421AA genotypes.

For carriers of the c. 521 CC or c. 421AA genotypes, the recommended maximum dose is Suvardio® It is 20 mg once a day (see the section “Pharmacokinetics”).

Concomitant therapy Rosuvastatin binds to various transport proteins (in particular, OATP1B1 and BCRP). Concomitant use of Suwardio® 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) (see the section “Interactions with other medicinal products”; please refer to the section “Interactions with other medicinal products”). follow the instructions for use of these medications before prescribing Suvardio®).

In such cases, the possibility of alternative therapy or temporary discontinuation of Suvardio should be evaluated. If the use of the above drugs is necessary, the benefit-risk ratio of concomitant therapy with Suvardio® should be evaluated and the possibility of reducing its dose should be considered.

Overdose

There is no specific treatment for rosuvastatin overdose.

In case of overdose, it is recommended to carry out symptomatic treatment and measures aimed at maintaining the function of vital organs and systems.

Monitoring of liver function and CKD activity is necessary. It is unlikely that hemodialysis will be effective.

Special instructions

Proteinuria (determined using test strips), mainly of tubular origin, was observed in patients receiving high doses of rosuvastatin, especially 40 mg, but in most cases it was intermittent or short-term. It has been shown that such proteinuria does not mean the occurrence of acute or progressive existing kidney disease. The incidence of severe renal impairment increases when taking 40 mg of rosuvastatin. It is recommended to monitor the parameters of renal function during therapy with rosuvastatin.

When using the drug Suvardio® myalgia, myopathy and, in rare cases, rhabdomyolysis were detected at all doses and, in particular, when taking the drug in a dose exceeding 20 mg. Very rarely, rhabdomyolysis occurred when ezetimibe was co-administered with HMG-CoA reductase inhibitors.

In this case, a pharmacological interaction of the drugs cannot be excluded, so Suwardio® and ezetimibe should be used together with caution.

The incidence of rhabdomyolysis increases with 40 mg of Suvardio.

Determination of CKD activity should not be performed after intense physical exertion or in the presence of other possible causes of increased CKD activity, which may lead to misinterpretation of the results obtained. If CPK activity is significantly increased before starting therapy (5 times higher than ULN), a second measurement should be performed after 5-7 days. Do not start therapy with Suvardio® if a repeated test confirms the initial activity of CPK (higher by more than 5 times compared to ULN).

Rosuvastatin, like other HMG-CoA reductase inhibitors, should be used with extreme caution in patients with existing risk factors for myopathy/rhabdomyolysis. These factors include:

• renal failure; • hypothyroidism (for a dose of 40 mg); • myopathy in history (including hereditary) (for doses of 40 mg); • a history of myotoxicity in patients receiving other inhibitors of HMG-COA reductase inhibitors or fibrates (for a dose of 40 mg); • alcohol abuse (for a dose of 40 mg); • the age of 65; • the state, accompanied by increase in the plasma concentration of rosuvastatin (for a dose of 40 mg); • concurrent use of fibrates (for doses of 40 mg).

In such patients, the risk-benefit ratio of therapy should be evaluated and clinical monitoring should be carried out throughout the course of therapy.

It is recommended to inform patients about the need to immediately inform the doctor about cases of unexpected occurrence of muscle pain, muscle weakness or spasms, especially in combination with malaise or fever!

In such patients, CPK activity should always be monitored. Treatment should be discontinued if CPK activity is more than 5 times the ULN or if muscle symptoms are severe and cause daily discomfort throughout the day (even if CPK activity is 5 times less than ULN). If symptoms disappear and CPK activity returns to normal, you should consider re-prescribing the drug or prescribing an alternative HMG-CoA reductase inhibitor in smaller doses, with careful monitoring of the patient. Regular monitoring of CPK activity in patients with no symptoms of rhabdomyolysis is impractical.

There were no signs of increased skeletal muscle adverse events when taking Suvardio® and concomitant therapy. However, an increase in the number of cases of myositis and myopathy was detected in patients taking other HMG-CoA reductase inhibitors together with fibrinic acid derivatives, including gemfibrozil, cyclosporine, nicotinic acid in lipid-lowering doses (more than 1 g / day), azole antifungal drugs, protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when co-administered with certain HMG-CoA reductase inhibitors. Therefore, simultaneous use of rosuvastatin and gemfibrozil is not recommended. It is necessary to carefully evaluate the risk – benefit ratio when rosuvastatin is co-administered with fibrates or nicotinic acid in lipid-lowering doses (more than 1 g / day). Concomitant use of rosuvastatin at a dose of 40 mg and fibrates is contraindicated. The drug Suvardio® it should not be prescribed to patients with acute, severe diseases, suspected myopathy or with possible development of secondary renal failure (for example, sepsis, arterial hypertension, surgery, trauma, metabolic syndrome, diabetes mellitus, seizures, endocrine disorders, water and electrolyte disorders).

In 2-4 weeks after the start of treatment and/or when increasing the dose of the drug, monitoring of lipid metabolism indicators is necessary (if necessary, dose adjustment is required).

Like other HMG-CoA reductase inhibitors, rosuvastatin should be used with extreme caution in patients who abuse alcohol or have a history of liver disease.

It is recommended to determine liver function indicators before and 3 months after the start of treatment. If the activity of” hepatic ” transaminases in the blood serum is 3 times higher than the upper limit of normal, you should stop taking the drug or reduce the dose taken. The frequency of severe liver function disorders (mainly associated with increased activity of “hepatic” transaminases) increases when taking 40 mg of the drug. In patients with secondary hypercholesterolemia due to hypothyroidism, nephrotic syndrome, therapy of the underlying disease should be carried out before starting treatment with rosuvastatin. Pharmacokinetic studies revealed an increase in the systemic concentration of rosuvastatin among patients of the Mongolian race compared to the data obtained among representatives of the Caucasian race.

Concomitant use of rosuvastatin with HIV protease inhibitors is not recommended.

Isolated cases of interstitial lung disease have been reported with the use of certain statins, especially for a long period of time. Symptoms of the disease may include shortness of breath, an unproductive cough, and poor overall health (weakness, weight loss, and fever). If interstitial lung disease is suspected, statin therapy should be discontinued.

In patients with a glucose concentration of 5.6 to 6.9 mmol / L, drug therapy was associated with an increased risk of developing type 2 diabetes mellitus.

Special precautions when disposing of an unused medicinal product

There is no need for special precautions when disposing of unused Suvardio®.

Influence on the ability to drive vehicles and mechanisms

Caution should be exercised when driving vehicles, engaging in potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions (risk of dizziness).

Product form

round biconvex film-coated tablets of brown color with the inscription “RSV 20” on one side.

Active ingredient

Rosuvastatin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets