Ozalex film-coated tablets 10 mg blister No. 28

Instructions for Ozalex film-coated tablets 10 mg blister No. 28

Composition

active ingredient: rosuvastatin;

1 film-coated tablet contains 10 mg or 20 mg or 40 mg of rosuvastatin calcium, expressed as rosuvastatin;

excipients: lactose monohydrate, microcrystalline cellulose, low-substituted hydroxypropylcellulose, colloidal anhydrous silicon dioxide, magnesium stearate, Opadry 03F84827 pink coating*;

*Opadry 03F84827 pink: hypromellose, titanium dioxide (E 171), red iron oxide (E 172), polyethylene glycol, talc.

Dosage form

Film-coated tablets.

Main physicochemical properties: pink film-coated tablets, round, biconvex, smooth on both sides.

Pharmacotherapeutic group

Lipid-lowering agents. HMG-CoA reductase inhibitors.

ATX code C10A A07.

Pharmacological properties

Pharmacodynamics.

Mechanism of action

Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a precursor of cholesterol. The primary site of action of rosuvastatin is the liver, the target organ for cholesterol reduction.

Rosuvastatin increases the number of low-density lipoprotein (LDL) receptors on the surface of liver cells, enhancing the uptake and catabolism of LDL, and inhibits the hepatic synthesis of very low-density lipoprotein (VLDL), thereby reducing the total number of VLDL and LDL particles.

Pharmacodynamic action

Rosuvastatin reduces elevated LDL-cholesterol, total cholesterol, and triglycerides and increases high-density lipoprotein cholesterol (HDL-C). It also reduces apoB, non-HDL-C, VLDL-C, VLDL-TG, and increases apoA-I.

Rosuvastatin also reduces the LDL-C/HDL-C, total-C/HDL-C, non-HDL-C/HDL-C, and apoB/apoA-I ratios.

The therapeutic effect is achieved within 1 week after the start of the drug, 90% of the maximum effect is achieved after 2 weeks. The maximum effect is usually achieved after 4 weeks and continues thereafter.

Pharmacokinetics.

Absorption

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

Distribution

Rosuvastatin is extensively absorbed by the liver, which is the main site of cholesterol synthesis and LDL-C clearance. The volume of distribution of rosuvastatin is approximately 134 L. Approximately 90% of rosuvastatin is bound to plasma proteins, primarily albumin.

Metabolism

Rosuvastatin undergoes minor metabolism (approximately 10%). In vitro metabolism studies using human hepatocytes indicate that rosuvastatin is a poor substrate for metabolism by cytochrome P450 enzymes. The main isoenzyme involved is CYP2C9, with 2C19, 3A4 and 2D6 playing a somewhat smaller role. The main identified metabolites are the N-desmethyl and lactone metabolites. The N-desmethyl metabolite is approximately 50% less active than rosuvastatin, the lactone metabolite is considered clinically inactive. Rosuvastatin accounts for more than 90% of the circulating HMG-CoA reductase inhibitory activity.

Breeding

Approximately 90% of the rosuvastatin dose is excreted unchanged in the feces (absorbed and unabsorbed active substance together), the rest is excreted in the urine. Approximately 5% is excreted in the urine in unchanged form. The half-life from blood plasma is approximately 19 hours and does not increase with increasing dose. The geometric mean clearance of the drug from blood plasma is approximately 50 l/h (coefficient of variation - 21.7%). As with other HMG-CoA reductase inhibitors, hepatic uptake of rosuvastatin occurs with the participation of the membrane transporter OATP-C, which plays an important role in the hepatic elimination of rosuvastatin.

Linearity

Systemic exposure to rosuvastatin increases in proportion to the dose. Pharmacokinetic parameters do not change with repeated daily administration.

Special patient groups

Age and gender

There was no clinically significant effect of age or gender on the pharmacokinetics of rosuvastatin in adults. The pharmacokinetics of rosuvastatin in children and adolescents with heterozygous familial hypercholesterolemia were similar to those in adult volunteers (see section "Children").

Race

Pharmacokinetic studies have shown that in patients of Mongoloid race (Japanese, Chinese, Filipinos, Vietnamese and Koreans) the median values of the area under the pharmacokinetic curve "concentration-time" (AUC) and Cmax are approximately twice as high as in Caucasians; in Indians the median values of AUC and Cmax are increased by approximately 1.3 times. Population pharmacokinetic analysis did not reveal any clinically significant differences between patients of Caucasian and Negroid races.

In a study in patients with varying degrees of renal impairment, no changes in plasma concentrations of rosuvastatin or the N-desmethyl metabolite were observed in subjects with mild or moderate renal impairment. In patients with severe renal impairment (creatinine clearance < 30 ml/min), plasma concentrations of rosuvastatin were 3-fold higher and the N-desmethyl metabolite was 9-fold higher than in healthy volunteers. Steady-state plasma concentrations of rosuvastatin in patients on hemodialysis were approximately 50% higher than in healthy volunteers.

Liver dysfunction

In a study of patients with varying degrees of hepatic impairment, there was no evidence of increased exposure to rosuvastatin in patients with Child-Pugh scores of 7 or less. However, two patients with Child-Pugh scores of 8 and 9 had systemic exposures that were at least twice as high as those in patients with lower scores. There is no experience with rosuvastatin in patients with Child-Pugh scores greater than 9.

Genetic polymorphism

The distribution of HMG-CoA reductase inhibitors, including rosuvastatin, occurs with the participation of transport proteins OATP1B1 and BCRP. Patients with genetic polymorphisms of SLCO1B1 (OATP1B1) and/or ABCG2 (BCRP) are at risk of increased exposure to rosuvastatin. In certain forms of the SLCO1B1 p.521СС and ABCG2 p.421АА polymorphisms, the AUC of rosuvastatin is increased compared to the SLCO1B1 p.521ТТ or ABCG2 p.421СС genotypes. Specific genotyping is not provided in clinical practice, but patients with such polymorphisms are recommended to use a lower daily dose of the drug Ozalex®.

Children

Two studies of the pharmacokinetics of rosuvastatin (tablets) in children with heterozygous familial hypercholesterolemia aged 10 to 17 years or aged 6 to 17 years showed that the drug exposure in children was lower than or similar to that in adult patients. The exposure of rosuvastatin was predictable according to the dose and duration of administration over 2 years of observation.

Indication

Treatment of hypercholesterolemia

Adults, adolescents and children aged 6 years and over with primary hypercholesterolemia (type IIa, including heterozygous familial hypercholesterolemia) or mixed dyslipidemia (type IIb) as an adjunct to diet when diet and other non-pharmacological measures (e.g. exercise, weight loss) are inadequate.

Adults, adolescents and children aged 6 years and over with homozygous familial hypercholesterolemia as an adjunct to diet and other lipid-lowering medicinal products (e.g. LDL apheresis) or in cases where such treatment is inappropriate.

Prevention of cardiovascular disorders

Prevention of major cardiovascular events in patients estimated to be at high risk of a first cardiovascular event (see section 5.1), as an adjunct to correction of other risk factors.

Contraindication

The drug Ozalex® is contraindicated:

– patients with hypersensitivity to rosuvastatin or to any of the excipients of the drug;

– patients with active liver disease, including persistent elevations of serum transaminases of unknown etiology and any elevation of serum transaminases greater than 3 times the upper limit of normal (ULN);

– patients with severe renal impairment (creatinine clearance < 30 ml/min);

– patients with myopathy;

– patients who were simultaneously receiving the combination of sofosbuvir/velpatasvir/voxilaprevir (see section “Interaction with other medicinal products and other types of interactions”);

– patients who are simultaneously receiving cyclosporine;

– during pregnancy and breastfeeding, as well as women of reproductive age who do not use adequate contraception.

The 40 mg dose is contraindicated in patients with a predisposition to myopathy/rhabdomyolysis.

Such risk factors include:

– moderate renal impairment (creatinine clearance < 60 ml/min);

– hypothyroidism;

– personal or family history of hereditary muscle diseases;

– history of myotoxicity with other HMG-CoA reductase inhibitors or fibrates;

– alcohol abuse;

– situations that may lead to an increase in the concentration of the drug in the blood plasma;

– belonging to the Mongoloid race;

– concomitant use of fibrates.

(See sections “Pharmacokinetics”, “Interaction with other medicinal products and other types of interactions” and “Special instructions for use”).

Interaction with other medicinal products and other types of interactions

Effect of concomitant medications on rosuvastatin

Transport protein inhibitors

Rosuvastatin is a substrate for several transport proteins, including the hepatic uptake transporter OATP1B1 and the efflux transporter BCRP. Concomitant use of rosuvastatin with medicinal products that inhibit these transport proteins may lead to increased plasma concentrations of rosuvastatin and an increased risk of myopathy (see sections 4.5 and 4.8, Dosage and Administration, Table).

During concomitant use of rosuvastatin and ciclosporin, rosuvastatin AUC values were on average approximately 7 times higher than those observed in healthy volunteers (see table). Rosuvastatin is contraindicated in patients receiving concomitant ciclosporin (see section "Contraindications").

Concomitant use did not affect the plasma concentration of cyclosporine.

Protease inhibitors

Although the exact mechanism of interaction is unknown, concomitant use of protease inhibitors may significantly increase rosuvastatin exposure (see table). For example, in a pharmacokinetic study, co-administration of 10 mg of rosuvastatin and a combination product containing two protease inhibitors (300 mg atazanavir/100 mg ritonavir) in healthy volunteers was accompanied by an increase in rosuvastatin AUC and Cmax by approximately 3 and 7 times, respectively. Concomitant use of rosuvastatin and some combinations of protease inhibitors is possible after careful consideration of dose adjustment of the drug Ozalex® due to the expected increase in rosuvastatin exposure (see sections “Interaction with other medicinal products and other forms of interaction”, “Special instructions for use” and “Method of administration and dosage”, table).

Gemfibrozil and other lipid-lowering agents

Concomitant use of rosuvastatin and gemfibrozil resulted in a 2-fold increase in rosuvastatin AUC and Cmax (see section "Special warnings and precautions for use").

Based on specific studies, no pharmacokinetically significant interaction with fenofibrate is expected, but a pharmacodynamic interaction is possible. Gemfibrozil, fenofibrate, other fibrates, and lipid-lowering doses (> or equal to 1 g/day) of niacin (nicotinic acid) increase the risk of myopathy when used concomitantly with HMG-CoA inhibitors, probably because they can cause myopathy when used alone. The 40 mg dose is contraindicated with concomitant use of fibrates (see sections 4.3 and 4.4). These patients should also be started on the 5 mg dose.

Ezetimibe

Concomitant administration of rosuvastatin 10 mg and ezetimibe 10 mg to patients with hypercholesterolemia resulted in a 1.2-fold increase in rosuvastatin AUC (see table). A pharmacodynamic interaction between rosuvastatin and ezetimibe, which could lead to adverse events, cannot be excluded (see section 4.4).

Antacid medications

Concomitant administration of rosuvastatin with antacid suspensions containing aluminum or magnesium hydroxide reduced the plasma concentration of rosuvastatin by approximately 50%. This effect was less pronounced when the antacid was administered 2 hours after rosuvastatin. The clinical significance of this interaction has not been studied.

Erythromycin

Concomitant use of rosuvastatin and erythromycin decreased rosuvastatin AUC by 20% and Cmax by 30%. This interaction may be due to increased intestinal motility due to erythromycin.

Ticagrelor

Ticagrelor may cause renal failure and may affect the renal excretion of rosuvastatin, increasing the risk of its accumulation. In some cases, the combined use of ticagrelor and rosuvastatin has led to decreased renal function, increased creatine phosphokinase (CPK) levels, and rhabdomyolysis. It is recommended to monitor renal function and CPK levels when ticagrelor and rosuvastatin are used concomitantly.

Cytochrome P450 enzymes

In vitro and in vivo studies have shown that rosuvastatin does not inhibit or induce cytochrome P450 isoenzymes. In addition, rosuvastatin is a weak substrate for these isoenzymes. Therefore, drug interactions resulting from P450-mediated metabolism are not expected. No clinically significant interactions were observed between rosuvastatin and fluconazole (an inhibitor of CYP2C9 and CYP3A4) or ketoconazole (an inhibitor of CYP2A6 and CYP3A4).

Interactions requiring dose adjustment of rosuvastatin (see also table)

If it is necessary to use rosuvastatin with other drugs that can increase its exposure, the dose of rosuvastatin should be adjusted. If the AUC of the drug is expected to increase by approximately 2 times or more, the use of rosuvastatin should be started at a dose of 5 mg 1 time per day. The maximum daily dose of rosuvastatin should be adjusted so that its expected exposure does not exceed the exposure observed when taking a dose of 40 mg / day without the use of drugs that interact with the drug; for example, when used with gemfibrozil, the dose of rosuvastatin will be 20 mg (an increase in exposure of 1.9 times), when used with the combination of ritonavir / atazanavir - 10 mg (an increase of 3.1 times).

If the drug increases the AUC of rosuvastatin by less than 2 times, the initial dose does not need to be reduced, but caution should be exercised when increasing the dose of Ozalex® to more than 20 mg.

Table

Effect of concomitant medications on rosuvastatin exposure

(AUC; in descending order of magnitude) from published clinical trial data

* Data presented as x-fold change represents the ratio between rosuvastatin in combination and alone. Data presented as % change represents the % difference relative to rosuvastatin alone.

Increase is indicated by the ↑ icon, decrease by the ↓ icon.

** Several interaction studies have been conducted at different doses of rosuvastatin, the most significant relationship is shown in the table.

Drugs/combinations that did not have a clinically significant effect on the AUC ratio of rosuvastatin when used simultaneously: aleglitazar 0.3 mg 7 days; fenofibrate 67 mg 7 days 3 times a day; fluconazole 200 mg 11 days 1 time a day; fosamprenavir 700 mg/ritonavir 100 mg 8 days 2 times a day; ketoconazole 200 mg 7 days 2 times a day; rifampin 450 mg 7 days 1 time a day; silymarin 140 mg 5 days 3 times a day.

Effect of rosuvastatin on concomitant medications

Vitamin K antagonists

As with other HMG-CoA reductase inhibitors, when starting or increasing the dose of rosuvastatin in patients receiving concomitant vitamin K antagonists (e.g. warfarin or another coumarin anticoagulant), an increase in the international normalized ratio (INR) may occur. Discontinuation of rosuvastatin or dose reduction may result in a decrease in INR. In such cases, appropriate monitoring of INR is advisable.

Oral contraceptives/hormone replacement therapy (HRT)

Concomitant use of rosuvastatin and oral contraceptives resulted in an increase in the AUC of ethinylestradiol and norgestrel by 26% and 34%, respectively. This increase in plasma levels should be taken into account when selecting the dose of oral contraceptives. There are no data on the pharmacokinetics of drugs in patients taking rosuvastatin and HRT simultaneously, so a similar effect cannot be excluded. However, the combination has been widely used in women in clinical trials and was well tolerated.

Other medicines

Digoxin

According to special studies, no clinically significant interaction with digoxin is expected.

Fusidic acid

Interaction studies of rosuvastatin with fusidic acid have not been conducted. The risk of myopathy, including rhabdomyolysis, may be increased by concomitant use of systemic fusidic acid with statins. The mechanism of this interaction (pharmacodynamic or pharmacokinetic, or both) is not yet clear. Rhabdomyolysis (including some fatal cases) has been reported in patients receiving this combination.

In patients in whom systemic fusidic acid is considered necessary, rosuvastatin treatment should be discontinued for the duration of fusidic acid treatment. See also section 4.4.

Children

Interaction studies have only been conducted in adults. The extent of interaction in children is unknown.

Application features

Effects on the kidneys

Proteinuria, detected by dipstick analysis and predominantly of tubular origin, has been observed in patients treated with higher doses of rosuvastatin, including 40 mg, and in most cases was transient or intermittent. Proteinuria was not a harbinger of acute or progressive renal disease (see section 4.8). The frequency of reports of serious renal events in post-marketing studies is higher with the 40 mg dose. Patients taking the drug at a dose of 40 mg should have their renal function checked regularly.

Effects on skeletal muscles

Skeletal muscle disorders, such as myalgia, myopathy and, rarely, rhabdomyolysis, have been reported in patients taking rosuvastatin at all doses, particularly above 20 mg. Very rare cases of rhabdomyolysis have been reported when ezetimibe was used in combination with HMG-CoA reductase inhibitors. The possibility of a pharmacodynamic interaction cannot be excluded (see section 4.5), and such a combination should therefore be used with caution.

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

Creatine kinase level

Creatine kinase (CK) levels should not be measured after significant exercise or in the presence of possible alternative causes of CK elevation that may complicate interpretation of results. If baseline CK levels are significantly elevated (>5 times ULN), repeat testing should be performed within 5–7 days to confirm the results. If repeat testing confirms baseline CK levels to be greater than 5 times ULN, treatment should not be initiated.

Before starting treatment

Rosuvastatin, like other HMG-CoA reductase inhibitors, should be administered with caution to patients with a predisposition to myopathy/rhabdomyolysis. Risk factors for this include:

– kidney dysfunction;

– hypothyroidism;

– personal or family history of hereditary muscle diseases;

– history of myotoxicity with other HMG-CoA reductase inhibitors or fibrates;

– alcohol abuse;

– age > 70 years;

– situations that may lead to an increase in the level of the drug in the blood plasma (see sections “Pharmacokinetics”, “Interaction with other medicinal products and other types of interactions” and “Method of administration and dosage”);

– concomitant use of fibrates.

In such patients, the risk of treatment should be weighed against the expected benefit; clinical monitoring is also recommended. If baseline CK levels are significantly elevated (>5 times ULN), treatment should not be initiated.

During treatment

Patients should be asked to report unexplained muscle pain, weakness or cramps immediately, especially if accompanied by malaise or fever. In such patients, CK levels should be measured. The drug should be discontinued if CK levels are significantly elevated (> 5 × ULN) or if muscle symptoms are severe and cause daily discomfort (even if CK levels are ≤ 5 × ULN). If symptoms resolve and CK levels return to normal, rosuvastatin or an alternative HMG-CoA reductase inhibitor may be restarted at the lowest dose and under close supervision.

There is no need to routinely monitor CK levels in asymptomatic patients. Very rare cases of immune-mediated necrotizing myopathy (IMNM) have been reported during or after treatment with statins, including rosuvastatin. Clinical manifestations of IMNM include proximal muscle weakness and elevated serum creatine kinase, which persist even after discontinuation of statins.

Rosuvastatin should not be used concomitantly with systemic fusidic acid or within 7 days of stopping fusidic acid. In patients in whom systemic fusidic acid is considered necessary, statin treatment should be discontinued for the duration of fusidic acid treatment. Rhabdomyolysis (including some fatal cases) has been reported in patients receiving the combination of fusidic acid and statins (see section 4.5).

Patients should be advised to seek immediate medical attention if they experience any symptoms of muscle weakness, pain or tenderness. Statin therapy may be resumed 7 days after the last dose of fusidic acid. In exceptional cases where prolonged systemic fusidic acid is required, e.g. for the treatment of severe infections, the need for concomitant use of rosuvastatin and fusidic acid should only be considered on a case-by-case basis and under close medical supervision.

Rosuvastatin should not be used in patients with acute, serious conditions that suggest myopathy or the possibility of developing renal failure due to rhabdomyolysis (sepsis, hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders or uncontrolled seizures).

Severe skin adverse reactions

Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and drug reaction with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal, have been reported with rosuvastatin. When prescribing rosuvastatin, patients should be informed of the signs and symptoms of severe cutaneous reactions and monitored closely. If signs and symptoms suggestive of these reactions appear, rosuvastatin should be discontinued immediately and alternative treatment should be considered.

If a patient develops a serious reaction such as SSRI or DRESS while taking Ozalex®, they should not be restarted on rosuvastatin in the future.

Effect on the liver

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

It is recommended to check biochemical indicators of liver function before starting treatment and 3 months later. Rosuvastatin should be discontinued or the dose reduced if the level of serum transaminases exceeds three times the upper limit of normal. The frequency of reports of serious hepatic events (mainly increased hepatic transaminases) in the post-marketing period was higher with the 40 mg dose.

In patients with secondary hypercholesterolemia due to hypothyroidism or nephrotic syndrome, the underlying disease should be treated first before initiating therapy with rosuvastatin.

Racial affiliation

Pharmacokinetic studies indicate an increase in exposure in patients of Mongoloid race by approximately twofold compared to Caucasians (see sections "Pharmacokinetics", "Contraindications" and "Method of administration and dosage").

Protease inhibitors

Increased systemic exposure to rosuvastatin has been observed in subjects receiving rosuvastatin concomitantly with various protease inhibitors in combination with ritonavir. The benefit of lipid-lowering effects of rosuvastatin in HIV patients receiving protease inhibitors should be considered, as well as the possibility of increased plasma concentrations of rosuvastatin at the start of therapy and with an increase in the dose of rosuvastatin in patients receiving protease inhibitors. Co-administration of the drug with some protease inhibitors is not recommended unless the dose of rosuvastatin is adjusted (see sections “Interaction with other medicinal products and other forms of interaction” and “Method of administration and dosage”).

Interstitial lung disease

Exceptional cases of interstitial lung disease have been reported with some statins, particularly with long-term treatment (see section 4.8). Symptoms may include dyspnoea, non-productive cough and general malaise (fatigue, weight loss and fever). If interstitial lung disease is suspected, statins should be discontinued.

Diabetes mellitus

There is some evidence that statins, as a class, increase blood glucose levels and in some patients at high risk of future diabetes, may cause hyperglycemia to a level requiring appropriate treatment of diabetes. However, this risk is outweighed by the reduced risk of vascular events with statins and should not be a reason to discontinue statin therapy. Patients at risk (fasting glucose 5.6–6.0 mmol/L, BMI > 30 kg/m2, elevated triglycerides, hypertension) should be monitored both clinically and biochemically according to national guidelines.

In the JUPITER study, the overall incidence of diabetes mellitus was 2.8% in the rosuvastatin group and 2.3% in the placebo group, predominantly in patients with fasting glucose levels between 5.6 and 6.9 mmol/L.

Assessment of linear growth (height), body weight, BMI (body mass index) and secondary Tanner puberty characteristics in children aged 6 to 17 years who took rosuvastatin is limited to a period of 2 years. After 2 years of study treatment, no effect on growth, body weight, BMI or puberty was observed (see section "Pharmacodynamics"). In a clinical study in children and adolescents who took rosuvastatin for 52 weeks, an increase in CK levels > 10 times the upper limit of normal and muscle symptoms after physical exertion or increased physical activity were observed more often compared to those in adults (see section "Adverse reactions").

Myasthenia gravis/ocular myasthenia

Several cases of de novo or exacerbation of pre-existing myasthenia gravis or ocular myasthenia have been reported with statins (see section 4.8). Ozalex® should be discontinued if symptoms worsen. Relapses have been reported with repeated use of the same or a different statin.

Excipients

This medicine contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

Use during pregnancy or breastfeeding

Rosuvastatin is contraindicated during pregnancy and breastfeeding.

Women of reproductive age should use adequate contraception.

Since cholesterol and other cholesterol biosynthesis products play an essential role in fetal development, the potential risk from inhibition of HMG-CoA reductase outweighs the benefits of using the drug during pregnancy. Animal data on reproductive toxicity are limited. If the patient becomes pregnant while taking this drug, treatment should be discontinued immediately.

Rosuvastatin is excreted in the milk of rats. There are no data on the excretion of rosuvastatin into human breast milk (see section "Contraindications").

Ability to influence reaction speed when driving vehicles or other mechanisms

Studies on the effect of rosuvastatin on the ability to drive and use machines have not been conducted. However, given the pharmacodynamic properties of the drug, it is unlikely that rosuvastatin will affect this ability. When driving or operating machinery, the possibility of dizziness should be taken into account during treatment.

Method of administration and doses

Before starting treatment, the patient should be placed on a standard cholesterol-lowering diet and should continue to follow it throughout treatment. The dose should be individualised according to the patient's response to treatment and the goals of therapy, in accordance with current guidelines.

Ozalex® can be taken at any time of the day, regardless of food intake.

Treatment of hypercholesterolemia

The recommended starting dose is 5* or 10 mg orally once daily for both statin-naïve patients and those switching from another HMG-CoA reductase inhibitor.

*Since the tablet is not divisible, if the drug is prescribed in a dose of less than 10 mg, rosuvastatin preparations with the possibility of such a dosage should be used.

When choosing the initial dose, the cholesterol level of each individual patient and the risk of cardiovascular disorders in the future should be taken into account, as well as the likelihood of developing undesirable reactions. If necessary, the dose can be increased to the next level after 4 weeks (see section "Pharmacodynamics"). Given that adverse reactions occur more often with the use of the drug in a dose of 40 mg than with lower doses (see section "Adverse reactions"), final titration of the dose to the maximum dose of 40 mg should only be done in patients with severe