Rosutatin

Rosuvastatin

Film-coated tablets

Pink, round, biconvex, film-coated tablets.

Each tablet contains:
Active ingredients: 10 mg rosuvastatin or 20 mg rosuvastatin (rosuvastatin calcium);
Excipients: microcrystalline cellulose, calcium phosphate, crospovidone, magnesium stearate, lactose monohydrate;
Shell composition: polyvinyl alcohol, polyethylene glycol (macrogol), titanium dioxide (E171), talc, yellow iron oxide (E172), red iron oxide (E172), carmoisine (azorubine) dye (E122), indigo blue dye (E132).

Lipid-lowering agents. HMG-CoA reductase inhibitors.

C10AA07

Rosuvastatin is a selective and competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), an enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a cholesterol precursor. The main target organ for lowering cholesterol levels is the liver.

Rosuvastatin increases the number of low-density lipoprotein (LDL) receptors on the cell surface, increasing the uptake and catabolism of LDL. It also inhibits the synthesis of very low density lipoproteins (VLDL) in liver cells, thereby reducing the total amount of LDL and VLDL.

Rosuvastatin reduces elevated levels of LDL cholesterol (LDL-C), total cholesterol and triglycerides (TG), increases high-density lipoprotein cholesterol (HDL-C), and also reduces the level of apolipoprotein B (ApoB), non-HDL-C, VLDL-C, VLDL-TG and increases the level of apolipoprotein A-I (ApoA-I). Rosuvastatin reduces the ratio of LDL-C/HDL-C, total cholesterol/HDL-C and non-HDL-C/HDL-C and ApoB/ApoA-I.

The therapeutic effect develops within 1 week after the start of treatment, after 2 weeks 90% of the maximum possible effect is achieved. The maximum therapeutic effect is usually achieved by the 4th week of therapy and is maintained with further use of Rosutatin.

• Primary hypercholesterolemia in adults, adolescents, and children over 6 years of age (type IIa, including familial heterozygous hypercholesterolemia) or mixed dyslipidemia (type IIb) as an adjunct to diet therapy when diet and other non-pharmacological treatments (e.g. exercise load, weight loss) are not effective enough;
• Familial homozygous hypercholesterolemia in adults, adolescents, and children over 6 years of age as an adjunct to diet therapy and other methods of lipid-lowering therapy (e.g. LDL apheresis), or in cases where such therapy is not effective enough;
• Prevention of severe cardiovascular complications in patients over 18 years of age, whose condition is assessed as a high risk of getting primary cardiovascular complications, as an addition to the correction of other risk factors.

Before starting therapy with Rosutatin, the patient must begin to follow a standard diet with a low cholesterol content, which must be followed throughout the treatment. The dose of Rosutatin should be selected individually depending on the goals of therapy and therapeutic response, taking into account the current generally accepted recommendations for target lipid concentrations.

This dosage form is not intended for initial therapy in the regimen of 5 mg once a day. For this purpose it is necessary to use another medicinal product that ensures achievement of the required single dose.

Tablets should be taken orally without chewing and drinking plenty of water. Rosutatin can be used at any time of the day, with or without meal.

The recommended initial dose of Rosutatin is 5 mg or 10 mg once a day, both for patients who have not previously taken statins, and for patients switched to taking Rosutatin after therapy with other HMG-CoA reductase inhibitors. When choosing an initial dose, it is necessary to take into account the initial individual cholesterol level and the possible risk of developing cardiovascular complications, as well as the potential risk of side effects.

If necessary, the dose of Rosutatin can be increased 4 weeks after the start of therapy. Due to the increased incidence of side effects when taking a dose of 40 mg, compared with lower doses of Rosutatin, the maximum dose of rosuvastatin 40 mg can only be prescribed to patients with severe hypercholesterolemia associated with a high risk of cardiovascular complications (especially in patients with familial hypercholesterolemia) who have not achieved the desired result of therapy when taking a dose of 20 mg, and who will be under medical supervision. Careful supervision of a specialist is recommended when increasing the dose of Rosutatin to 40 mg.

Use in children
The use of Rosutatin in children and adolescents should be carried out only under control of specialists.

Children and adolescents from 6 to 17 years old
Familial heterozygous hypercholesterolemia
In children and adolescents with familial heterozygous hypercholesterolemia, the recommended starting dose is 5 mg daily.

In children aged 6-9 years with familial heterozygous hypercholesterolemia, the usual dose range is 5-10 mg per day orally. The safety and efficacy of doses greater than 10 mg per day have not been studied in this group.

In children and adolescents 10 to 17 years of age with heterozygous hereditary hypercholesterolemia, the recommended dose range is 5-20 mg once daily. The safety and efficacy of doses greater than 20 mg per day have not been studied in this group.
Dose titration should be carried out according to individual response and tolerability in pediatric patients in accordance with recommendations for pediatric treatment. Children and adolescents should be given a standard cholesterol-lowering diet prior to starting treatment with rosuvastatin, and this diet should be continued during treatment with rosuvastatin.

Familial homozygous hypercholesterolemia
In children and adolescents aged 6 to 17 years with familial homozygous hypercholesterolemia, the recommended maximum dose is 20 mg per day.

A starting dose of 5 to 10 mg once daily is recommended, depending on age, weight, and prior statin use. Dose titration up to a maximum dose of 20 mg once daily should be done according to individual response and tolerability in pediatric patients, in accordance with pediatric guidelines. Children and adolescents should be given a standard cholesterol-lowering diet prior to starting treatment with rosuvastatin, and this diet should be continued during treatment with rosuvastatin. In this category of patients, there is limited experience with doses above 20 mg.

Children under the age of 6
The safety and efficacy of Rosutatin in children under 6 years of age have not been studied. In this regard Rosutatin is not recommended for treatment of children under 6 years of age.

The 40 mg dose should not be prescribed to children and adolescents.

Elderly patients
For patients older than 70 years, the recommended initial dose of Rosutatin is 5 mg. There is no need for other changes in the dosing regimen in this group of patients.

Patients with impaired renal function
For patients with mild to moderate renal impairment, no change in dosing regimen is required. For patients with moderate renal impairment (CC less than 60 ml/min), the recommended initial dose of Rosutatin is 5 mg. The use of Rosutatin at a dose of 40 mg is contraindicated in patients with moderate renal impairment (creatinine clearance less than 60 ml/min). In patients with severe renal insufficiency (CC less than 30 ml/min) any dose Rosutatin is contraindicated.

Patients with impaired liver function
An increase in the systemic concentration of rosuvastatin in patients with liver failure with 7 or less points according to the Child-Pugh classification was not detected. However, an increase in systemic concentration was noted in patients whose condition was estimated at 8 and 9 points according to the Child-Pugh classification. In these patients, renal function should be assessed. There is no experience of using Rosutatin in patients with more than 9 points according to the Child-Pugh classification. Rosutatin is contraindicated in patients with liver disease in the active phase.

Ethnic groups
In patients of the Mongoloid race, an increase in the systemic exposure of rosuvastatin is possible. The recommended initial dose of Rosutatin for this group of patients is 5 mg. The use of Rosutatin at a dose of 40 mg is contraindicated in such patients.

Genetic polymorphism
Some types of genetic polymorphism are known to increase exposure to rosuvastatin. In patients with these types of genetic polymorphisms, a lower daily dose of rosuvastatin is recommended.

Patients with predisposition to myopathy
The recommended starting dose is 5 mg for patients with predisposing factors for myopathy. The use of Rosutatin at a dose of 40 mg is contraindicated in such patients.

Concomitant therapy
Rosuvastatin is a substrate for various transport proteins (e.g. OATP1B1 and BCRP). The risk of myopathy (including rhabdomyolysis) is increased when rosuvastatin is co-administered with medicinal products that may increase plasma concentrations of rosuvastatin due to interactions with these transport proteins (e.g. cyclosporine, and some protease inhibitors, including combinations of ritonavir with atazanavir, lopinavir, and/or tipranavir (see Sections Interaction with other medicines and Warnings and precautions). If possible, consider alternative medicines and, if necessary, consider temporarily stopping rosuvastatin. In cases where co-administration of these medicinal products with rosuvastatin is necessary, the benefits and risks of concomitant therapy should be carefully considered, as well as the dose adjustment of rosuvastatin.

As with other HMG-CoA reductase inhibitors, the incidence of side effects is dose-dependent. Frequency of side effects: very common (≥ 1/10); common (≥ 1/100, but < 1/10); uncommon (≥ 1/1000, but < 1/100); rare (≥ 1/10000 but < 1/1000), very rare (< 1/10000). Based on clinical trial data and post-marketing experience, the following side effects have been reported:

Blood and lymphatic system disorders: thrombocytopenia (rare).

Immune system disorders: hypersensitivity reactions, including angioedema (rare).

Metabolism disorders: type 2 diabetes mellitus (common). The incidence of diabetes depends on the presence or absence of risk factors (fasting plasma glucose ≥ 5.6 mmol/l, body mass index > 30 kg/m², elevated triglycerides, history of hypertension).

Mental disorders: depression (frequency unknown).

Nervous system disorders: headache, dizziness (common); polyneuropathy, memory loss (very rare); peripheral neuropathy, sleep disturbances, including insomnia and nightmares (frequency unknown).

Respiratory, thoracic and mediastinal disorders: cough, shortness of breath (frequency unknown).

Gastrointestinal disorders: constipation, nausea, abdominal pain (common); pancreatitis (rare); diarrhea (frequency unknown).

Hepatobiliary disorders: an increase in the concentration of transaminases in the blood serum (rare); jaundice, and hepatitis (very rare).

Skin and subcutaneous tissue disorders: skin rash, pruritus, and urticarial (uncommon); Stevens-Johnson syndrome (frequency unknown).

Musculoskeletal and connective tissue disorders: myalgia (common); myopathy including myositis, and rhabdomyolysis (rare); arthralgia (very rare); tendon injuries, sometimes complicated by rupture, immune-mediated necrotizing myopathy (frequency unknown).

Renal and urinary disorders: hematuria (very rare).

Reproductive system and breast disorders: gynecomastia (very rare).

General disorders and administration site conditions: asthenia (common); edema (frequency unknown).

Similar to other HMG-CoA reductase inhibitors, the incidence of adverse reactions associated with rosuvastatin therapy is dose-dependent.

Renal and urinary disorders: Proteinuria has been observed in some patients treated with rosuvastatin. Proteinuria was diagnosed by urinalysis using indicator strips. In most cases, it was of tubular origin. Changes in protein content from ‘complete absence’ and ‘traces’ to ‘++’ or more were observed in less than 1% of patients taking rosuvastatin at a dose of 10 or 20 mg, and also in approximately 3% of patients taking Rosutatin at a dose of 40 mg. Minimal changes in the protein content in the urine from ‘complete absence’ and ‘traces’ to ‘+’ were found in patients from the rosuvastatin 20 mg therapy group. As a rule, against the background of ongoing treatment, proteinuria decreased or disappeared on its own. A review of the results of clinical studies and post-marketing data did not reveal a causal relationship between proteinuria and kidney disease (acute or progressive).

Hematuria has been found in some patients taking rosuvastatin. The results of clinical studies indicate its low prevalence.

Musculoskeletal and connective tissue disorders: skeletal muscle side effects (e.g. myalgia, myopathy including myositis, and, rarely, rhabdomyolysis with or without acute renal failure) have been observed in patients who received rosuvastatin regardless of dosages, mainly in doses greater than 20 mg.

In some patients taking rosuvastatin, a dose-dependent increase in the concentration of creatine kinase was found. In most cases, this phenomenon was mild, asymptomatic and transient. If the concentration of creatine kinase exceeds the upper limit of the norm by more than 5 times, then treatment with rosuvastatin should be discontinued.

Hepatobiliary disorders: As with other HMG-CoA reductase inhibitors, a dose-dependent increase in hepatic transaminases was observed in a small number of patients taking rosuvastatin. In most cases, it was mild, asymptomatic and transient.

The following side effects have been reported with some statins: sexual dysfunction, interstitial lung disease, especially with long-term therapy (in exceptional cases).

The frequency of rhabdomyolysis development, severe disorders of the kidneys and liver (mainly represented by an increase in the transaminases concentration) is higher when using Rosutatin at a dose of 40 mg.

Children
During clinical trials in children and adolescents taking rosuvastatin for 52 weeks, increased creatine kinase concentration (> 10 times the upper limit of normal), muscle symptoms after exercise or after increased physical activity were observed more often compared with observations during clinical trials in adults. With respect to other reactions, the safety profile of rosuvastatin in children and adolescents is similar to that in adults.

Reporting adverse reactions
If you experience any adverse reactions, please consult your healthcare provider. This recommendation applies to any possible adverse reactions, including those not listed in this leaflet. By reporting your adverse reactions, you help to get more information about Rosutatin.

• Hypersensitivity to rosuvastatin or to any other component of Rosutatin;
• Liver disease in the active phase (including a persistent increase in serum transaminase activity, as well as any increase in serum transaminase activity by more than 3 times compared to the upper limit of normal concentration);
• Severe liver dysfunction;
• Severe renal dysfunction (creatinine clearance less than 30 ml/min);
• Lactose intolerance, lactase deficiency or glucose-galactose malabsorption (Rosutatin contains lactose);
• Myopathy;
• Simultaneous reception of cyclosporine;
• Pregnancy, lactation, in women of childbearing age in the absence of adequate methods of contraception.

Rosutatin in a daily dose of 40 mg is contraindicated in patients with factors predisposing to the development of myopathy (rhabdomyolysis). These factors include:

• Moderate renal dysfunction (creatinine clearance less than 60 ml/min);
• Hypothyroidism;
• Presence of an individual or family history of muscle diseases;
• History of toxic effects on the muscles when taking other inhibitors of HMG-CoA reductase or fibrates;
• Alcohol abuse;
• Situations in which an increase in the concentration of rosuvastatin in plasma is possible;
• Belonging to the Mongoloid race;
• Simultaneous reception of fibrates.

When taking a larger dose than prescribed by a healthcare provider, immediately seek medical advice for timely medical assistance!

There is no specific treatment for an overdose of rosuvastatin. In case of overdose, symptomatic and supportive treatment is recommended. Liver function and serum creatine kinase concentration should be monitored. The effectiveness of hemodialysis is unlikely.

If you miss the next dose of Rosutatin, then you should not compensate for the missed dose by taking a double dose, just take the usual dose of Rosutatin. With irregular use of Rosutatin, the effectiveness of treatment decreases.

It is not recommended to stop taking Rosutatin without consulting your healthcare provider. Termination of treatment with Rosutatin is possible if pregnancy is detected, side effects from the skeletal muscles (muscle weakness and/or pain), hypersensitivity reactions (oedema of face soft tissues, lips, and/or tongue; breathing or swallowing problems; itching, and/or rash). When you stop taking Rosutatin, concentration of cholesterol in the blood may increase again.

Transport protein inhibitors: Rosuvastatin is a substrate of various transport proteins (including OATP1B1 and BCRP). Simultaneous prescription of rosuvastatin with medicines that are inhibitors of these transport proteins can lead to an increase in concentration of rosuvastatin in the blood plasma, and an increase in the risk of myopathy (see Section Dosage and administration).

Cyclosporine: with simultaneous use of rosuvastatin and cyclosporine, the AUC of rosuvastatin was approximately 7 times higher than with monotherapy with Rosutatin in healthy volunteers. Rosuvastatin is contraindicated in patients receiving concomitant therapy with cyclosporine (see Section Contraindications). The concomitant use of rosuvastatin and cyclosporine was not accompanied by changes in the concentration of cyclosporine in the blood plasma.

HIV protease inhibitors: when rosuvastatin is coadministered with atazanavir/ritonavir or lopinavir/ritonavir combinations, the dose of rosuvastatin should not exceed 10 mg once daily.

Although the exact mechanism of interaction is unknown, co-administration of protease inhibitors can lead to a significant increase in the concentration of rosuvastatin. In a pharmacokinetic study on the simultaneous use of 10 mg rosuvastatin and a combination of two protease inhibitors (300 mg lopinavir/100 mg ritonavir) in healthy volunteers, an approximately three-fold and seven-fold increase in the AUC and C_max of rosuvastatin, respectively, was found. Concomitant use of rosuvastatin and certain combinations of protease inhibitors is possible after a decision has been made to change the dosing regimen in accordance with the expected increase in exposure to rosuvastatin.

Gemfibrozil and other lipid-lowering agents: concomitant use of gemfibrozil and rosuvastatin was accompanied by a two-fold increase in C_max and AUC of rosuvastatin.

According to the results of special studies of interaction with other medicinal products, a pharmacokinetically significant interaction with fenofibrate is unlikely, but a pharmacodynamic interaction is possible. Gemfibrozil, fenofibrate, other fibrates, and lipid-lowering doses of nicotinic acid (more than 1 g/day) increase the risk of developing myopathy when used simultaneously with HMG-CoA reductase inhibitors, possibly due to the fact that they alone can cause myopathy. The prescription of a dose of 40 mg is contraindicated with the concomitant use of fibrates. With concomitant fibrate therapy, the initial dose of rosuvastatin should be 5 mg.

Ezetimibe: Co-administration of rosuvastatin 10 mg and ezetimibe 10 mg resulted in a 1.2-fold increase in rosuvastatin AUC in patients with hypercholesterolemia. Pharmacodynamic interactions between rosuvastatin and ezetimibe, leading to the development of adverse reactions, cannot be excluded.

Antacids: simultaneous use of rosuvastatin and an antacid suspension containing aluminum or magnesium hydroxide leads to a decrease in the plasma concentration of rosuvastatin by approximately 50%. This effect was reduced when taking antacids 2 hours after the administration of rosuvastatin. The clinical significance of this interaction has not been studied.

Erythromycin: combined use of rosuvastatin and erythromycin resulted in a decrease in the AUC and C_max of rosuvastatin by 20% and 30%, respectively. This may be due to the fact that erythromycin increases the peristalsis of the gastrointestinal tract.

Enzymes of the cytochrome P450 group: rosuvastatin is neither an inhibitor nor an inducer of enzymes of the cytochrome P450 system. In addition, rosuvastatin is a non-core substrate for these enzymes. There was no clinically significant interaction between rosuvastatin and fluconazole (an inhibitor of CYP2C9 and CYP3A4) and ketoconazole (an inhibitor of CYP2A6 and CYP3A4). Combined use of rosuvastatin and itraconazole (a CYP3A4 inhibitor) increases the AUC of rosuvastatin by 28% (clinically insignificant). Thus, interaction with other medicinal products, associated with drug metabolism mediated by isoenzymes of the cytochrome P450 system, is unlikely.

Interaction with drugs that require a change in the rosuvastatin dosing regimen (see Table 1): the dosing regimen of Rosutatin should be changed, if it is necessary to use it together with medicines that increase the exposure of rosuvastatin. If an increase in exposure (AUC) of 2 times or more is expected, then the initial dose of rosuvastatin should be 5 mg once a day. The maximum daily dose of rosuvastatin should be selected so that the expected AUC of rosuvastatin does not exceed that for a daily dose of 40 mg taken without simultaneous administration of agents that interact with rosuvastatin. For example, the maximum daily dose of rosuvastatin when taken with gemfibrozil is 20 mg (increase in AUC by 1.9 times). With a combination of ritonavir/atazanavir it is 10 mg (increase in AUC by 3.1 times).

Table 1. Effect of concomitant therapy on rosuvastatin exposure (AUC, data in descending order of value), based on published clinical trial data

* Some drug interaction studies have been performed using different dosages of rosuvastatin, the table shows the most pronounced changes in AUC.

Vitamin K antagonists: as with other HMG-CoA reductase inhibitors, the initiation of treatment or an increase in the dose of rosuvastatin in patients receiving concomitant vitamin K antagonists (for example, warfarin) may lead to an increase in the international normalized ratio (INR). Discontinuation or dose reduction of rosuvastatin may lead to a decrease in INR. In such cases, monitoring of INR is recommended.

Oral contraceptives / hormone replacement therapy: simultaneous use of rosuvastatin and oral contraceptives was accompanied by an increase in AUC of ethinylestradiol and norgestrel by 26% and 34%, respectively. An increase in the concentration of these hormones in the blood plasma must be taken into account when selecting the dose of oral contraceptives. Pharmacokinetic data characterizing the use of rosuvastatin against the background of hormone replacement therapy are not available. Therefore, the occurrence of such an effect cannot be ruled out. However, this combination of medicines is widely used in clinical trials and is well tolerated by women.

Digoxin: no clinically significant interaction of rosuvastatin with digoxin is expected.

Fusidic acid: interactions between rosuvastatin and fusidic acid have not been studied. As with other statins, post-marketing reports of musculoskeletal side effects, including rhabdomyolysis (sometimes lethal), have been reported with concomitant use of rosuvastatin and fusidic acid. In this regard, simultaneous use of rosuvastatin and fusidic acid is not recommended. If possible, it is recommended to temporarily stop treatment with rosuvastatin. If it is impossible to stop therapy with rosuvastatin, careful monitoring of the patient is necessary.

Your healthcare provider must be informed about all medicines you are taking. Talk to your healthcare provider before taking any medicine while taking Rosutatin.

Renal disorders
Proteinuria, predominantly of tubular origin, has been detected by dipstick testing in patients taking high doses of rosuvastatin, especially 40 mg, and has been transient or intermittent in most cases. Proteinuria does not predict the development of an acute kidney disease or progression of an existing kidney disease. In the post-marketing period, serious renal impairment was more often observed in patients taking rosuvastatin at a dose of 40 mg. As part of the standard examination of patients receiving Rosutatin at a dose of 40 mg, it is necessary to evaluate renal function.

Musculoskeletal disorders
Skeletal muscle side effects (myalgia, myopathy and, less commonly, rhabdomyolysis) have been observed in patients treated with rosuvastatin at any dose, especially at doses exceeding 20 mg. In very rare cases, rhabdomyolysis has been observed in patients receiving ezetimibe in combination with HMG-CoA reductase inhibitors. A pharmacodynamic interaction of these medicines cannot be ruled out and caution should be exercised when they are used together.

As with other HMG-CoA reductase inhibitors, in the post-marketing period, the incidence of rhabdomyolysis with rosuvastatin was higher in patients taking rosuvastatin at a dose of 40 mg.

Determination of creatine kinase concentration
Determination of the concentration of creatine kinase should not be carried out after intense physical exertion or in the presence of other reasons for the increase in its concentration, which may lead to incorrect interpretation of the results. With an initially high concentration of creatine kinase (> 5 times the upper limit of normal), a second study should be performed after 5-7 days. Treatment should not be started if a repeat study confirms an elevated creatine kinase concentration (> 5 times the upper limit of normal).

Fusidic acid
Rosutatin tablets should not be co-administered with fusidic acid for systemic use or within 7 days of discontinuation of fusidic acid. In patients requiring fusidic acid treatment, rosuvastatin should be discontinued throughout the entire treatment period. Rhabdomyolysis (sometimes lethal) has been reported in patients co-treated with rosuvastatin and fusidic acid. Patients should be informed that they should seek immediate medical attention if they develop muscle weakness, pain, or muscle tenderness.

7 days after taking of the last dose of fusidic acid, treatment with rosuvastatin can be restarted.

In exceptional cases, when long-term treatment with fusidic acid is necessary, for example, in severe infections, the decision on the need for the combined use of fusidic acid and rosuvastatin should be made individually, weighing the potential risk of therapy and the possible benefit with careful monitoring of the patient’s condition.

Before treatment
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:

• impaired renal function;
• hypothyroidism;
• muscle disorders in the patient’s history or family history;
• history of toxic effects on the muscles when taking other inhibitors of HMG-CoA reductase or fibrates;
• alcohol abuse;
• age over 70;
• situations in which it is possible to increase the concentration of rosuvastatin in plasma;
• combined use with fibrates.

In such patients, the risk-benefit ratio of therapy should be considered, and inpatient monitoring throughout the course of treatment is recommended. If the initial concentration of creatine kinase exceeds 5 times the normal level, then treatment should not be started.

During treatment
The patient should be warned about the need to immediately inform the doctor about cases of sudden onset of muscle pain, muscle weakness or spasms, especially in combination with malaise and fever. In such patients, the concentration of creatine kinase should be determined. Therapy should be discontinued if the concentration of creatine kinase exceeds the upper limit of the norm by more than 5 times, or if the muscle symptoms are pronounced and cause daily discomfort (even if the concentration of creatine kinase does not exceed the upper limit of the norm by 5 times). If the symptoms disappear and the creatine kinase concentration returns to normal, consideration should be given to re-prescribing rosuvastatin or other HMG-CoA reductase inhibitors at the lowest dose with careful monitoring of the patient. Routine monitoring of creatine kinase levels in the absence of symptoms of rhabdomyolysis is inappropriate.

There are rare reports of the development of immune-mediated necrotizing myopathy associated with the use of statins, including rosuvastatin. Immune-mediated necrotizing myopathy is characterized by proximal muscle weakness and elevated creatine kinase levels that persist after discontinuation of statin treatment.

An increase in the incidence of myositis and myopathy has been reported in patients taking other HMG-CoA reductase inhibitors together with fibric acid derivatives, including gemfibrozil, cyclosporine, nicotinic acid, azole antifungals, protease inhibitors, and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when co-administered with certain HMG-CoA reductase inhibitors. Thus, simultaneous use of rosuvastatin and gemfibrozil is not recommended. With the combined use of rosuvastatin and fibrates or nicotinic acid, the ratio of the risk of side effects and the possible benefit of changing lipid levels should be taken into account. With concomitant therapy with fibrates, taking rosuvastatin at a dose of 40 mg is contraindicated.

It is not recommended to take rosuvastatin in combination with fusidic acid. Rhabdomyolysis has been reported in patients receiving rosuvastatin concomitantly with fusidic acid.

Rosutatin should not be used to treat patients with acute, serious disorders suggestive of myopathy or predisposing to renal failure secondary to rhabdomyolysis (e.g. sepsis, hypotension, surgery, trauma, severe metabolic, endocrine or electrolyte disturbances, and uncontrolled convulsions).

Liver disorders
As with other HMG-CoA reductase inhibitors, Rosutatin should be used with extreme caution in patients who abuse alcohol or have a history of liver disease. It is recommended to conduct a study of liver function before starting treatment and 3 months after the start of treatment. If the concentration of transaminases in the blood serum is 3 times the upper limit of normal, you should stop taking Rosutatin or reduce the dose of Rosutatin. The frequency of side effects related to the liver (associated mainly with an increase in the concentration of transaminases in the blood serum) increases when taking Rosutatin at a dose of 40 mg.

In patients with secondary hypercholesterolemia due to hypothyroidism or nephrotic syndrome, therapy of the underlying disease should be carried out before treatment with Rosutatin.

Racial origin
Pharmacokinetic studies have shown an increase in the exposure of rosuvastatin in representatives of the Mongoloid race compared with representatives of the Caucasian race (see Sections Dosage and administration and Pharmacological properties).

Protease inhibitors
Combined use with protease inhibitors is not recommended (see Section Interaction with other medicines).

Special information on excipients
Rosutatin contains lactose, so it is contraindicated in patients with hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.

Interstitial lung disease
In exceptional cases, interstitial lung disease has been reported with the use of some statins, especially with long-term treatment. Shortness of breath, dry cough, and deterioration in overall health (weakness, weight loss, and fever) may also occur. If interstitial lung disease is suspected, statin therapy should be discontinued.

Diabetes
Some evidence suggests that statins as a class increase glucose levels and, in patients at high risk of developing diabetes, can cause blood sugar levels to rise to the extent that appropriate treatment is required. However, the benefits of statins in reducing the risk of cardiovascular disease outweigh the small increase in the risk of developing diabetes, so statin use should not be discontinued. There are reasons for periodic monitoring of glycemia in patients at risk (fasting glucose 5.6 – 6.9 mmol/L, body mass index > 30 kg/m2, increased triglycerides, hypertension), according to approved recommendations.

In the JUPITER clinical trial, the incidence of diabetes mellitus was 2.8% in the rosuvastatin group, and 2.3% in the placebo group. Most patients had fasting blood glucose levels of 5.6–6.9 mmol/L.

If you have diabetes or are at high risk of developing diabetes and you are taking statins, your healthcare provider will monitor your condition. If you have high blood sugar, overweight and high blood pressure, you are at a high risk of developing diabetes.

Children
Assessment of linear height, weight, body mass index, and secondary characteristics of puberty on the Tanner scale in children aged 6 to 17 years taking rosuvastatin is limited to a period of 2 years. After 2 years of the study, no effect of rosuvastatin treatment on height, weight, body mass index or puberty was found (see Section Pharmacological properties).

In clinical trials in children and adolescents taking rosuvastatin for 52 weeks, increases in creatine kinase (> 10 times the upper limit of normal), muscle symptoms after exercise or after increased physical activity are observed more often compared with observations during clinical trials in adults (see Section Possible side effects).

If you have one of the diseases or conditions listed above, be sure to consult your healthcare provider before taking Rosutatin.

Rosutatin is contraindicated for use during pregnancy and during breast-feeding.

Women of reproductive age should use reliable and adequate methods of contraception.

Since cholesterol and other products of cholesterol biosynthesis are important for fetal development, the potential risk of HMG-CoA reductase inhibition outweighs the benefit Rosutatin therapy in pregnant women. Animal studies provide only limited data on reproductive toxicity. If pregnancy occurs in a woman taking rosuvastatin, Rosutatin should be stopped immediately.

Rosuvastatin has been found in the breast milk of rats. Data on the allocation of rosuvastatin with breast milk in humans are not available.

Studies of the effect of rosuvastatin on the ability to drive vehicles and use mechanisms have not been conducted. However, given the pharmacodynamic characteristics of Rosutatin, caution should be exercised when driving vehicles or using other mechanical means (dizziness may occur during treatment with rosuvastatin).

15 tablets per blister made of three-layer film (PVC/PE/PVDC) or two-layer colorless film (PVC/PVDC) and flexible packaging based on aluminum foil. Two blister packs No. 15 with a patient information leaflet in an outer carton.

Protect from light and moisture. Store at a temperature not exceeding 25°C.
Keep out of the reach of children.

2 years. Do not use after the expiry date.

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Phone / Fax +375 17 268 63 64
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To report adverse reactions use the electronic application form on the manufacturer’s website: https://academpharm.by/en