Suvardio, 10 mg 28 pcs.

Pharmacotherapeutic group:

Hypolipidemic drug – HMG-CoA reductase inhibitor.

The ATX code: C10AA07.

Pharmacological properties

Pharmacodynamics

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

Rosuvastatin increases the number of LDL receptors on the surface of hepatocytes, which increase the capture and catabolism of LDL, and inhibits the liver synthesis of very low density lipoproteins (VLDL), thus reducing 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 decreases the concentration of apolipoprotein B (ApoB), non-HDL-C, HDL-C, TG-LDL-C and increases the concentration of apolipoprotein A-1 (ApoA-1) (see Table 1), decreases the ratio of LDL-C/HC-LDL, total CH/LC-LDL and non-LC-LDL/CC-LDL and the apoB/apoA-1 ratio.

After the start of therapy with rosuvastatin therapeutic effect appears within one week, after 2 weeks of treatment it reaches 90% of the maximum possible effect. Maximum therapeutic effect is usually reached 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 their race, sex or age, including patients with diabetes and familial hypercholesterolemia.
In 80% of patients with hypercholesterolemia of type IIa and IIb according to Fredrickson classification (mean baseline concentration of LDL-C about 4.8 mmol/l) when using rosuvastatin at a dose of 10 mg, LDL-C concentration reaches values less than 3 mmol/l.
In patients with heterozygous familial hypercholesterolemia who took rosuvastatin in doses from 20 to 80 mg according to the scheme of forced dose titration, a positive dynamics of lipid profile parameters was observed. After titration of daily dose up to 40 mg per day (12 weeks of therapy) 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 in doses of 20 and 40 mg, the average decrease in LDL-C concentration was 22%.

Additive effect was noted in combination with fenofibrate for TG concentration and with nicotinic acid (more than 1 g per day) for HDL-C concentration.

. Patients with low risk of coronary heart disease (CHD) (Framingham Scale risk less than 10% over 10 years), with a mean LDL-C concentration of 4.0 mmol/L (154.5 mg/dL) and subclinical atherosclerosis, which was assessed by carotid intima-media complex (CTIM) thickness, rosuvastatin at a dose of 40 mg/day significantly slowed the rate of progression of maximum CTIM for 12 carotid segments compared with placebo at a rate of – 0.0145 mm/year (95% confidence interval (CI): -0.0196 to – 0.0093, at p < 0.0001). The dose of 40 mg should only be administered to patients with significant hypercholesterolemia and high risk of cardiovascular disease.

Pharmacokinetics

Absorption
Maximum concentration (Cmax) of rosuvastatin in plasma is reached approximately 5 h after oral administration.
Absolute bioavailability is ≈20%.

Distribution
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 is bound to plasma proteins, mainly to albumin.

Metabolism
A limited amount of rosuvastatin (approximately 10%) undergoes biotransformation.
Metabolism of rosuvastatin is insignificantly associated with isoenzymes of cytochrome P450 system. CYP2C9 is the main isoenzyme involved in metabolism of rosuvastatin, while CYP2C19, CYP3A4 and CYP2D6 are less involved in 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 pharmacological activity on inhibition of circulating HMG-CoA reductase is provided by rosuvastatin, the rest by its metabolites.

Elimation
Approximately 90% of the administered dose of rosuvastatin is excreted unchanged through the intestine (including absorbed and unabsorbed rosuvastatin), the remaining part is excreted by the kidneys. About 5% of the administered drug dose is excreted unchanged by the kidneys. The elimination half-life (T1/2) is 19 h, it does not change when increasing the drug dose. Mean geometric plasma clearance is approximately 50 l/h (coefficient of variation 21.7%). As with other HMG-CoA reductase inhibitors, the membrane membrane-bound cholesterol transporter is involved in the “hepatic” uptake of rosuvastatin. This transporter plays a major role in the excretion of rosuvastatin by the liver.

Linearity
Systemic exposure to rosuvastatin increases in proportion to the dose. There are no changes in pharmacokinetic parameters after multiple daily doses of the drug.

Genetic polymorphism
HMK-CoA reductase inhibitors, including rosuvastatin, bind to the transport proteins OATP1B1 (organic anion transport polypeptide involved in the capture of statins by hepatocytes) and BCRP (efflux transporter). Carriers of SLCO1B1 (OATP1B1) C.521CC and ABCG2 (BCRP) C.421AA genotypes had 1.6 and 2.4-fold increased exposure (AUC – area under the “concentration-time” curve) to rosuvastatin compared with SLCO1B1c.521TT and ABCG2 c.421AA genotypes, respectively.

Special patient populations
Age and sex
Age and sex have no clinically significant effect on the pharmacokinetic parameters of rosuvastatin.

Ethnic groups
Pharmacological studies have shown an approximately two-fold increase in median AUC and Cmax of rosuvastatin in patients of the mongoloid race (Japanese, Chinese, Filipino, Vietnamese and Koreans) compared to those of the Caucasian race; median AUC and Cmax increased approximately 1.3-fold in Hindu patients. At the same time the analysis of pharmacokinetic parameters for all studied population showed no clinically significant differences in pharmacokinetics of the drug among representatives of 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 insufficiency (creatinine clearance (CK) less than 30 ml/min) the plasma concentration of rosuvastatin is 3 times higher, and N-desmethylrosuvastatin concentration is 9 times higher than in healthy volunteers. Plasma concentrations of rosuvastatin in patients on hemodialysis are approximately 50% higher than in healthy volunteers.

Hepatic failure
In patients with varying degrees of hepatic failure with a Child-Pugh score of 7 or lower no increase in T1/2 of rosuvastatin was found. However, in 2 patients with Child-Pugh scores 8 and 9 there was observed prolongation of T1/2, approximately 2 times more than in patients with lower Child-Pugh scores. There is no experience with rosuvastatin in patients with a Child-Pugh score above 9.

Indications

• primary hypercholesterolemia according to the Fredrickson classification (type IIa, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb) as an addition to diet when diet and other non-drug treatments are insufficient;
• familial homozygous hypercholesterolemia as an adjunct to diet and other lipid-lowering therapy (eg, LDL apheresis), or in cases where such therapy is not sufficiently effective;
• hypertriglyceridemia (type IV according to the Fredrickson classification) as an addition to the diet;
• to slow the progression of atherosclerosis as an addition to diet in patients who are indicated for therapy to reduce the concentration of total cholesterol and LDL-cholesterol.
• 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 concentration HDL-C, smoking, family history of early onset CAD).

Pharmacological effect

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 into mevalonate, a cholesterol precursor. Rosuvastatin acts on the liver, where the synthesis of cholesterol (CH) and the catabolism of low-density lipoproteins (LDL) take place.

Rosuvastatin increases the number of LDL receptors on the surface of hepatocytes, which enhance the uptake and catabolism of LDL, and inhibits the liver’s synthesis of very low-density lipoproteins (VLDL), 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), non-HDL-C, VLDL-C, TG-VLDL 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 non-HDL-C/HDL-C 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 week 4 and is maintained with regular use of the drug.

Clinical effectiveness
Rosuvastatin is effective in adult patients with hypercholesterolemia, with or without hypertriglyceridemia, regardless of race, gender or age, including patients with diabetes mellitus and familial hypercholesterolemia.
In 80% of patients with type IIa and IIb hypercholesterolemia according to the Fredrickson classification (average initial LDL-C concentration of about 4.8 mmol/l), when using rosuvastatin at a dose of 10 mg, the LDL-C concentration reaches values ​​of less than 3 mmol/L.
In patients with heterozygous familial hypercholesterolemia who took rosuvastatin in doses from 20 to 80 mg according to a forced dose titration scheme, positive dynamics of lipid profile parameters were noted. After titrating 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 in doses of 20 and 40 mg, the average reduction in LDL-C concentration was 22%.

An 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 risk 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 carotid intima-media thickness (IMT), rosuvastatin at a dose of 40 mg/day significantly slowed the rate of progression of maximum IMT for 12 carotid artery segments compared with placebo at a rate of -0.0145 mm/year (95% confidence interval (CI): -0.0196 to -0.0093, with p < 0.0001). The 40 mg dose should be prescribed only to patients with severe hypercholesterolemia and a high risk of developing cardiovascular disease.

Pharmacokinetics

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

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

Metabolism
A limited amount of rosuvastatin undergoes biotransformation (approximately 10%).
The metabolism of rosuvastatin is to a small extent associated with isoenzymes of the cytochrome P450 system. The CYP2C9 isoenzyme is the main isoenzyme involved in the metabolism of rosuvastatin, while the CYP2C19, CYP3A4 and CYP2D6 isoenzymes are involved in metabolism to a lesser extent.

The main identified metabolites of rosuvastatin are N-dismethyl rosuvastatin and lactone metabolites.
N-desmethyl rosuvastatin is approximately 50% less active than rosuvastatin; the lactone metabolites are pharmacologically inactive. More than 90% of the pharmacological activity of inhibiting circulating HMG-CoA reductase is provided by rosuvastatin, the rest is provided by its metabolites.

Removal
Approximately 90% of the dose of rosuvastatin is excreted unchanged through the intestines (including absorbed and unabsorbed rosuvastatin), the remainder is excreted by the kidneys. About 5% of the administered dose of the drug is excreted unchanged by the kidneys. The half-life (T1/2) is 19 hours and does not change with increasing doses of the drug. The geometric mean plasma clearance is approximately 50 L/h (coefficient of variation 21.7%). As is the case with other HMG-CoA reductase inhibitors, the membrane cholesterol transporter across membranes 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 of rosuvastatin increases in proportion to the dose. After repeated daily administration of the drug, no changes in pharmacokinetic parameters occur.

Genetic polymorphism
Inhibitors of HMC-CoA reductase, including rosuvastatin, bind to the transport proteins OATP1B1 (organic anion transport polypeptide involved in the uptake of statins by hepatocytes) and BCRP (efflux transporter). Carriers of genotypes SLCO1B1 (OATP1B1) C.521CC and ABCG2 (BCRP) C.421AA showed an increase in exposure (AUC – area under the concentration-time curve) of rosuvastatin by 1.6 and 2.4 times, respectively, compared with carriers of 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 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 to those in Caucasians; Indian patients showed an approximately 1.3-fold increase in median AUC and Cmax. At the same time, 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 Negroid races.

Kidney 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 the blood plasma is 3 times higher, and the concentration of N-desmethylrosuvastatin is 9 times higher than in healthy volunteers. Plasma concentrations of rosuvastatin in hemodialysis patients are approximately 50% higher than in healthy volunteers.

Liver failure
In patients with varying degrees of liver failure with a score of 7 and below 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, T1/2 prolongation was noted, approximately 2 times higher than that for patients with lower scores on the Child-Pugh scale. There is no experience with the use of rosuvastatin in patients with a score above 9 on the Child-Pugh scale.

Special instructions

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

When using the drug Suwardio® in all doses and, in particular, when taking the drug in a dose exceeding 20 mg, myalgia, myopathy and, in rare cases, rhabdomyolysis were identified. Rhabdomyolysis has occurred very rarely with concomitant use of ezetimibe and HMG-CoA reductase inhibitors.

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

The incidence of rhabdomyolysis increases when taking 40 mg of Suwardio®.

Determination of CPK activity should not be carried out after intense physical activity or in the presence of other possible reasons for increased CPK activity, which may lead to incorrect interpretation of the results obtained. If CPK activity is significantly increased before the start of therapy (5 times higher than ULN), a repeat measurement should be taken after 5-7 days. You should not start therapy with Suwardio® if a repeat test confirms the initial CPK activity (more than 5 times higher than the ULN).

Rosuvastatin, like other HMG-CoA reductase inhibitors, should be prescribed 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);
• a history of myotoxicity while taking other HMG-CoA reductase inhibitors or fibrates (for a dose of 40 mg);
• alcohol abuse (for a dose of 40 mg);
• age over 65 years;
• conditions accompanied by an increase in plasma concentration of rosuvastatin (for a dose of 40 mg);
• simultaneous use of fibrates (for a dose of 40 mg).

In such patients, the balance of risk and possible benefit of therapy should be assessed and clinical monitoring should be carried out throughout the entire course of therapy.

It is recommended that patients be informed to immediately notify their doctor if they experience unexpected muscle pain, muscle weakness, or cramps, especially when accompanied by malaise or fever!
In such patients, it is imperative to monitor CPK activity. 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 the ULN). If symptoms resolve and CPK activity returns to normal, restarting the drug or prescribing an alternative HMG-CoA reductase inhibitor in lower doses should be considered with careful monitoring of the patient. Regular monitoring of CK activity in patients in the absence of symptoms of rhabdomyolysis is impractical.

There were no signs of an increase in adverse events from skeletal muscles when taking the drug 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 fibric acid derivatives, including gemfibrozil, cyclosporine, nicotinic acid in lipid-lowering doses (more than 1 g/day), azole antifungals, protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when combined with certain HMG-CoA reductase inhibitors. Therefore, simultaneous use of rosuvastatin and gemfibrozil is not recommended. It is necessary to carefully evaluate the balance of risk and possible benefit when using rosuvastatin together 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.
Suwardio® should not be administered to patients with acute, severe illness, suspected myopathy, or possible development of secondary renal failure (for example, sepsis, hypertension, surgery, trauma, metabolic syndrome, diabetes mellitus, seizures, endocrine disorders, fluid and electrolyte disturbances).

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

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

It is recommended to measure liver function parameters before and 3 months after the start of treatment. If the activity of “liver” 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 dysfunction (associated mainly with increased activity of “liver” transaminases) increases when taking 40 mg of the drug. In patients with secondary hypercholesterolemia due to hypothyroidism, nephrotic syndrome, therapy for 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 Mongoloid race compared to 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 some statins, especially over long periods of time. Manifestations of the disease may include shortness of breath, non-productive cough and deterioration in general health (weakness, loss of body weight and fever). If interstitial lung disease is suspected, statin therapy should be discontinued.

In patients with glucose concentrations from 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 unused medicinal product

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

Impact on the ability to drive vehicles and machinery

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

Active ingredient

Rosuvastatin

Composition

1 tablet 10 mg contains:

active ingredient:

rosuvastatin calcium in terms of rosuvastatin – 10,000 mg;

excipients:

anhydrous lactose – 53.690 mg;

colloidal silicon dioxide anhydrous – 0.330 mg;

microcrystalline cellulose, silicated – 27,500 mg;

dry corn starch – 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; talc – 0.180 mg; talc (polishing agent)² – 0.057 mg.

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 “liver” transaminases, as well as any increase in the activity of “liver” transaminases in the blood serum by more than 3 times compared with the upper limit of normal (ULN);
• severe renal dysfunction (creatinine clearance less than 30 ml/min);
• myopathy;
• simultaneous use of cyclosporine;
• pregnancy, breastfeeding period;
• use in patients predisposed to the development of myotoxic complications;
• lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome (the drug contains lactose);
• age under 18 years (efficacy and safety have not been established).

With caution

For a daily dose of 5 mg, 10 mg and 20 mg: there is a risk of developing myopathy/rhabdomyolysis – renal failure, hypothyroidism; personal or family history of hereditary muscle diseases and previous history of muscle toxicity when using other HMG-CoA reductase inhibitors (statins) or fibrates; excessive alcohol consumption; conditions in which an increase in plasma concentration of rosuvastatin is noted; age over 65 years; high risk of developing diabetes; history of liver disease; sepsis; arterial hypotension; extensive surgical interventions; injuries; severe metabolic, endocrine or water-electrolyte disorders; uncontrolled epilepsy; race (Mongoloid race); simultaneous use 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 (<1/10000); frequency unknown - based on available data, it was not possible to determine the frequency of occurrence.

Blood and lymphatic system disorders
frequency unknown: thrombocytopenia.

Immune system disorders
rarely: hypersensitivity reactions, including angioedema.

Endocrine system disorders
often: type 2 diabetes mellitus.

Central nervous system disorders
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;
rarely: pancreatitis;
frequency unknown: diarrhea.

Skin disorders
uncommon: skin itching, rash, urticaria;
frequency unknown: Stevens-Johnson syndrome.

Laboratory indicators
Increased activity of creatine phosphokinase (CPK), concentration of glucose, glycosylated hemoglobin, bilirubin in the blood plasma, activity of gamma-glutamyl transpeptidase, alkaline phosphatase, dysfunction of the thyroid gland.

Other
often: asthenic syndrome, gynecomastia, peripheral edema.
Disorders of the urinary system
very rare: hematuria.

Proteinuria may occur when taking rosuvastatin. Changes in urinary protein (from absent to trace amounts to level ++ or higher) are observed in less than 1% of patients taking rosuvastatin at doses 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 as a change from a zero level or the presence of traces to a + level, was observed when taking the drug at a dose of 20 mg. In most cases, proteinuria decreased and resolved spontaneously during treatment. Analysis of clinical trial data did not reveal a causal relationship between proteinuria and acute or progressive kidney disease.

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

Disorders of the liver and biliary tract
rarely: increased activity of liver transaminases;
very rarely: jaundice, hepatitis.

Side effects reported with some statins include depression, sleep disturbances including insomnia and nightmares, and sexual dysfunction.

Interaction

With simultaneous use of rosuvastatin and cyclosporine, the AUC of rosuvastatin was on average 7 times higher than the value observed in healthy volunteers. The combined use of these drugs leads to an 11-fold increase in the concentration of rosuvastatin in the blood plasma, while the plasma concentration of cyclosporine does not change (see section “Contraindications”).
When using other statins, reports of cases of rhabdomyolysis have been received with the simultaneous use of rosuvastatin and fusidic acid; monitoring of the patient’s condition is necessary; if necessary, temporary discontinuation of rosuvastatin may be possible.

As with other HMG-CoA reductase inhibitors, initiating rosuvastatin therapy or increasing the dose of the drug in patients receiving concomitant vitamin K antagonists (eg, warfarin or other coumarin anticoagulants) may result in an increase in the international normalized ratio (INR). Discontinuation or reduction of the dose of rosuvastatin may cause a decrease in MHO. In such cases, MHO monitoring should be performed.

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

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 CPK activity is necessary. Hemodialysis is unlikely to be effective.

Manufacturer

Lek d.d., Slovenia