rosuvastatin | Suvardio tablets is covered.pl.ob. 10 mg 28 pcs.

Pharmacological action

Pharmacotherapeutic group:

lipid-lowering 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 precursor to cholesterol. Rosuvastatin acts on the liver, where the synthesis of cholesterol (cholesterol) and the catabolism of low density lipoproteins (LDL) are carried out.

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 cholesterol-lipoproteins (HDL-C), and also reduces the concentration of apolipoprotein B (ApoL), C, not HS-VLDL, TG-VLDLP and increases the concentration of apolipoprotein A-1 (ApoA-1) (see table 1), reduces the ratio of LDL-C / HDL-C, total cholesterol / HDL-C and HDL / HDL-C and the ratio of ApoB / ApoA-1.

After starting therapy with rosuvastatin, the therapeutic effect appears within one week, after 2 weeks of treatment 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.

Table 1. The dependence of the response to treatment on the dose of rosuvastatin in patients with primary hypercholesterolemia (Fredrickson types IIa and IIb) (mean adjusted percentage change relative to the initial concentration)

Dose, mg Number of patients

sHLV-C Placebo13-7-53-3-7-30

517-45-3313-35-44-384

1017-52-3614-10-48-424

2017-55-408-23-51-465

4018- 63-4610-28-60-540

Clinical efficacy of

Rosuvastatin is effective in adult patients with hypercholesterolemia, with or without hypertriglyceridemia, independently and from their race, gender or age, including in patients with diabetes mellitus and familial hypercholesterolemia.

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

In patients with heterozygous familial hypercholesterolemia who took rosuvastatin in doses of 20 to 80 mg according to the forced dose titration scheme, positive dynamics of lipid profile was observed. After titrating a daily dose of up 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 in 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) (risk on the Framingham scale of less than 10% for a period of more than 10 years), with an average concentration of LDL cholesterol of 4.0 mmol / l (154.5 mg / dl) and subclinical atherosclerosis, which was evaluated by the thickness of the intima-media complex of carotid arteries (TCIM), rosuvastatin at a dose of 40 mg / day significantly slowed the progression rate of 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 -0.0196 to - 0.0093, with p <0.0001). A dose of 40 mg should be prescribed only to patients with severe hypercholesterolemia and a high risk of developing cardiovascular disease.

Pharmacokinetics

Absorption of

The maximum concentration (Cmax) of rosuvastatin in plasma is reached approximately 5 hours after ingestion.

Absolute bioavailability is 20 %.

Distribution of

Rosuvastatin is metabolized primarily 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 with albumin.

Metabolism

Biotransformation undergoes a limited amount of rosuvastatin (approximately 10%).

Rosuvastatin metabolism is slightly related to isoenzymes of the cytochrome P450 system. The isoenzyme CYP2C9 is the main isoenzyme involved in the metabolism of rosuvastatin, while the isoenzymes 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, lactone metabolites are pharmacologically inactive. More than 90% of the pharmacological activity in inhibiting circulating HMG-CoA reductase is provided by rosuvastatin, the rest is metabolites.

Excretion

Approximately 90% of the dose of rosuvastatin taken is excreted unchanged through the intestines (including absorbed and unabsorbed rosuvastatin), the remainder is excreted by the kidneys. Unchanged by the kidneys, about 5% of the administered dose of the drug is excreted. The half-life (T1 / 2) is 19 hours it does not change with an increase in the dose of the drug. The geometric mean plasma clearance is approximately 50 l / h (coefficient of variation 21.7%). As with other HMG-CoA reductase inhibitors, the membrane carrier of cholesterol through membranes is involved in the process of “hepatic” uptake of rosuvastatin. This carrier plays a large role in the excretion of rosuvastatin by the liver.

Linearity

Systemic exposure of rosuvastatin increases in proportion to dose. After repeated daily administration of the drug, changes in pharmacokinetic parameters do not occur.

Genetic polymorphism

Inhibitors of GMK-CoA reductase, including rosuvastatin, bind to transport proteins OATP1B1 (a polypeptide of transport of organic anions involved in the capture of statins by hepatocytes) and BCRP (efflux transporter). In carriers of the SLCO1B1 (OATP1B1) C.521CC and ABCG2 (BCRP) C.421AA genotypes, an increase in exposure (AUC is the area under the concentration – time curve) of rosuvastatin was 1.6 and 2.4 times, respectively, compared with 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 showed an approximately twofold increase in the median AUC and Cmax of rosuvastatin in patients of the Mongoloid race (Japanese, Chinese, Filipinos, Vietnamese and Koreans) compared with those in the Caucasoid race in Indian patients, an increase in the median AUC and Cmax in approximately 1.3 times. Moreover, the analysis of pharmacokinetics for the entire study population did not reveal clinically significant differences in the pharmacokinetics of the drug among representatives of the Caucasoid and Negroid races.

Renal failure

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

Hepatic insufficiency

In patients with various degrees of liver failure with a score of 7 or lower on the Child-Pugh scale, no increase in T1 / 2 of rosuvastatin was detected. However, in 2 patients with scores of 8 and 9 on the Child-Pugh scale, an elongation of T1 / 2 was observed, approximately 2 times higher than the same indicator for patients with lower values ​​on the Child-Pugh scale. There is no experience with the use of rosuvastatin in patients with a score higher than 9 on the Child-Pugh scale.

Indications

• primary hypercholesterolemia according to the Fredrickson classification (type IIa, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb) as a supplement to the diet, when the diet and other non-pharmacological treatment methods are hyperlastic cholesterolemia diet and other lipid-lowering therapy (e.g., LDL-apheresis), or in cases when such therapy is not effective enough

• hypertriglyceridemia (type IV according to the Fredrickson classification) as an addition to the

diet • to slow the progression of atherosclerosis as an addition to the diet in patients who are shown 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 (older than 50 years in men over 60 years old) in women, an increased concentration of C-reactive protein ( 2 mg / l) in the presence of at least one additional risk factor, such as arterial hypertension, low concentration of HDL-C, smoking, family history of early onset of CHD).

Contraindications

• hypersensitivity to rosuvastatin or any of the components of the drug

• liver disease in the active phase, including a persistent increase in the activity of “liver” transaminases, as well as any increase in the activity of “liver” transaminases in blood serum more than 3 times compared with the upper limit of normal (VGN)

• severe renal impairment (CC less than 30 ml / min)

•

myopathy • simultaneous administration of cyclosporine

• pregnancy, breastfeeding

• use in patients predisposed to the development of myotoxic complications

• lactase deficiency, lactose intolerance, glucose-galactose malabsorbts syndrome ii (the drug contains lactose)

• age under 18 years (efficacy and safety not established).

Precautions

For daily doses of 5 mg, 10 mg and 20 mg: there is a risk of myopathy / rhabdomyolysis - renal failure, hypothyroidism is a personal or family history of hereditary muscle diseases and a previous history of muscle toxicity with other HMG-CoA reductase inhibitors (statins) or fibrates, excessive alcohol consumption, with an increased plasma concentration of rosuvastatin over 65 years old, a high risk of developing liver disease diabetes history of sepsis arterial hypotension extensive surgery trauma severe metabolic, endocrine or water-electrolytes dysregulation uncontrolled epilepsy race (Mongoloid race), concomitant use of fibrates.

Use during pregnancy and lactation

The drug Suvardio® is contraindicated for use during pregnancy and during breastfeeding. Women of reproductive age should use reliable and adequate contraceptives.

Since cholesterol and cholesterol biosynthesis products are important for fetal development, the potential risk of inhibiting HMG-CoA reductase exceeds the benefits of its use in pregnancy.

If you are diagnosing pregnancy, you should immediately stop taking Suvardio®.

There are no data on the allocation of rosuvastatin with breast milk. If it is necessary to prescribe the drug Suvardio® during lactation, it is necessary to decide on the termination of breastfeeding.

Special instructions

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

When using SuvardioВ® in all doses, and especially when taking the drug in a dose exceeding 20 mg, myalgia, myopathy and, in rare cases, rhabdomyolysis. Very rarely rhabdomyolysis occurred while taking ezetimibe and HMG-CoA reductase inhibitors.

In this case, the pharmacological interaction of the drugs cannot be ruled out, therefore, the drug SuvardioВ® and ezetimibe should be used with caution.

The incidence of rhabdomyolysis when taking 40 mg of SuvardioВ® is increased.

Determination of CPK activity should not be carried out after intense physical exertion or if there are other possible reasons for the increase in CPK activity, which may lead to an incorrect interpretation of the results. If the activity of CPK before the start of therapy is significantly increased (5 times higher than VGN), after 5-7 days, a second measurement should be carried out. You should not start therapy with SuvardioВ®, if a repeated test confirms the initial activity of CPK (more than 5 times higher compared with VGN).

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

• renal failure

• hypothyroidism (for a dose of 40 mg)

• history of myopathy (including hereditary) (for a dose of 40 mg)

• history of myotoxicity while taking other HMG-inhibitors CoA reductase or fibrate (for a dose of 40 mg)

• alcohol abuse (for a dose of 40 mg)

• age 65+

• conditions accompanied by an increase in plasma concentration of rosuvastatin (for a dose of 40 mg)

• concomitant use of fibrate (for a dose 40 mg).

In such patients, the ratio of risk and the possible benefits of therapy should be assessed and clinical observation should be carried out throughout the course of therapy.

It is recommended that patients be informed of the need to immediately inform the doctor of cases of sudden onset of muscle pain, muscle weakness or cramping, especially in combination with malaise or fever!

In such patients, it is imperative to monitor the activity of KFK. Treatment should be discontinued if KFK activity is more than 5 times higher than VGN or if muscle symptoms are pronounced and cause daily discomfort throughout the day (even if KFK activity is 5 times less than VGN). If symptoms disappear and CPK activity returns to normal, consideration should be given to re-prescribing the drug or prescribing an alternative inhibitor of HMG-CoA reductase in lower doses with careful monitoring of the patient. Regular monitoring of CPK activity in patients in the absence of symptoms of rhabdomyolysis is impractical.

There were no signs of an increase in adverse events from skeletal muscle when taking SuvardioВ® and concomitant therapy. However, an increase in the incidence of myositis and myopathy was detected in patients taking other HMG-CoA reductase inhibitors together with fibric acid derivatives, including gemfibrozil, cyclosporine, nicotinic acid in lipid lowering doses (more than 1 g / day), azole antifungal drugs, and protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when combined with certain HMG-CoA reductase inhibitors. Therefore, the simultaneous administration of rosuvastatin and gemfibrozil is not recommended. It is necessary to carefully evaluate the ratio of risk and possible benefits when combined with rosuvastatin and fibrates or nicotinic acid in lipid lowering doses (more than 1 g / day). The concomitant use of rosuvastatin in a dose of 40 mg and fibrates is contraindicated.

SuvardioВ® should not be prescribed to patients with acute, severe illness, with suspected myopathy, or with possible development of secondary renal failure (e.g., sepsis, arterial hypertension, surgery, trauma, metabolic syndrome, diabetes mellitus, convulsions, endocrine disorders, water electrolyte disturbances).

2-4 weeks after the start of treatment and / or with an increase in the dose of the drug, monitoring of lipid metabolism is necessary (dose adjustment is necessary if necessary).

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

It is recommended that liver function tests be determined before and 3 months after the start of treatment. If the activity of “liver” transaminases in blood serum is 3 times higher than the upper limit of normal, you should stop taking the drug or reduce the dose. The frequency of severe liver dysfunction (associated mainly with an increase in the activity of “liver” transaminases) increases with 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 treatment with rosuvastatin.

Pharmacokinetic studies have shown an increase in systemic concentrations of rosuvastatin among patients of the Mongoloid race compared with data obtained among representatives of the Caucasian race.

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

When using certain statins, especially over a long period of time, isolated cases of interstitial lung disease have been reported. Manifestations of the disease can include shortness of breath, unproductive cough, and general well-being (weakness, weight loss, and fever). If interstitial pulmonary 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 type 2 diabetes.

Special precautions when disposing of an unused drug

No special precautions are required when disposing of an unused drug SuvardioВ®.

Impact on the ability to drive vehicles, mechanisms

Care must be taken when driving vehicles, engaging in potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions (risk of dizziness).

Composition

1 tablet of 10 mg contains: active ingredient: calcium rosuvastatin in terms of rosuvastatin - 10,000 mg excipients: anhydrous lactose - 53.690 mg silica colloidal anhydrous - 0.330 mg microcrystalline cellulose, dry silica - 16,500 mg talc - 1.100 mg sodium stearyl 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 tal K - 0.180 mg talc (polishing agent) - 0.057 mg.

Side effects

According to the World Health Organization (WHO), adverse reactions are classified according to their frequency of development as follows: very often (? 1/10), often (? 1/100, <1/10), infrequently (? 1/1000, <1/100), rarely (? 1/10000, <1/1000) and very rarely (<1/10000) the frequency is unknown - according to the available data, it was not possible to establish the frequency of occurrence.

Disorders of the blood and lymphatic system

frequency unknown: thrombocytopenia.

Immune system disorders

rare: hypersensitivity reactions, including angioedema.

Disorders of the endocrine system

often: type 2 diabetes.

Disorders of the central nervous system

often: headache, dizziness

very rare: polyneuropathy, memory loss.

Respiratory system disorders

frequency unknown: cough, shortness of breath.

Digestive system disorders

often: constipation, nausea, abdominal pain

rare: pancreatitis

frequency unknown: diarrhea.

Disorders of the skin

infrequently: skin itching, rash, urticaria

frequency unknown: Stevens-Johnson syndrome.

Laboratory indicators

Increased activity of creatine phosphokinase (CPK), concentration of glucose, glycosylated hemoglobin, bilirubin in blood plasma, activity of gamma-glutamyl transpeptidase, alkaline phosphatase, impaired thyroid function.

Other

often: asthenic syndrome, gynecomastia, peripheral edema.

Urinary system disorders

very rare: hematuria.

Proteinuria may be observed with rosuvastatin. Changes in protein in the urine (from absence to trace amounts to ++ and above) are observed in less than 1% of patients taking rosuvastatin at a dose of 10 mg and 20 mg, and about 3% of patients taking the drug at a dose of 40 mg . A slight change in the amount of protein in the urine, expressed as a change from zero level or the presence of traces to level +, was observed when taking the drug at a dose of 20 mg. In most cases, proteinuria decreased and passed independently during treatment. An analysis of clinical trial data did not reveal a causal relationship between proteinuria and acute or progressive kidney disease.

Disorders of the musculoskeletal system and connective tissue

often: myalgia

rare: myopathy (including myositis), rhabdomyolysis

very rare: arthralgia

frequency unknown: immuno-mediated necrotizing myopathy.

Disorders from the liver and biliary tract

rare: increased activity of ԬiverԠtransaminases

very rare: jaundice, hepatitis.

Some side effects of these statins have been reported, like: depression, sleep disturbance, including insomnia and nightmares, sexual dysfunction.

Drug Interactions

With the simultaneous use of rosuvastatin and cyclosporine AUC, rosuvastatin was on average 7 times higher than that observed in healthy volunteers. The combined use of these drugs leads to an increase in the concentration of rosuvastatin in blood plasma by 11 times, while the plasma concentration of cyclosporine does not change (see section "Contraindications").

When using other statins, reports of cases of rhabdomyolysis with the simultaneous use of rosuvastatin and fusidic acid were received, monitoring of the patient's condition is necessary, if necessary, a temporary cessation of rosuvastatin is possible.

As with other HMG-CoA reductase inhibitors, initiating rosuvastatin therapy or increasing the dose in patients receiving simultaneously vitamin K antagonists (e.g. warfarin or other coumarin anticoagulants) can lead to an increase in the international normalized ratio (MHO). Cancellation or reduction of the dose of rosuvastatin may cause a decrease in MHO. In such cases, MHO should be monitored.

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

Overdose of

There is no specific treatment for an overdose of rosuvastatin.

In case of overdose, it is recommended to carry out symptomatic treatment and activities aimed at maintaining the function of vital organs and systems. It is necessary to control liver function and CPK activity. Hemodialysis is unlikely to be effective.

Storage conditions

In the original packaging in a dry place at a temperature not exceeding 25 РC.

Keep out of the reach of children!

Expiration

2 years.

Do not use the medicine after the expiry date stated on the packaging!

Active ingredient

Rosuvastatin



pharmacy terms and conditions for prescription

Form of Treatment

tablets