Cardiolip, 5 mg 90 pcs

Pharmacotherapeutic group

Hypolipidemic drug – HMG-CoA-reductase inhibitor

ATX Code

C10AA

Pharmacodynamics:

The hypolipidemic drug is a selective competitive inhibitor of the enzyme HMG-CoA reductase converting 3-hydroxy-3-methylglutaryl-CoA to mevalonate cholesterol (CH) precursor. The main target of rosuvastatin action is the liver where the synthesis of cholesterol and catabolism of low-density lipoproteins (LDL) take place. Rosuvastatin increases number of LDL receptors on liver cell surface increasing capture and catabolism of LDL that in its turn leads to inhibition of synthesis of very low density lipoproteins (VLDL) thus reducing total amount of LDL and LDL.

. Rosuvastatin decreases elevated concentrations of LDL cholesterol (LDL-C) total cholesterol (TC) triglycerides (TG) increases concentrations of high-density lipoprotein cholesterol (HDL-CH1VP) and decreases concentrations of apolipoprotein B (ApoB) HC-LDL-TG-LDL and increases apolipoprotein A-I concentration (ApoA-I).

As a result of the action of rosuvastatin there is a decrease in the atherogenicity coefficient (index), which characterizes the improvement of lipid profile in patients with hypercholesterolemia.

The atherogenicity index = (BCA – HDL-C) / HDL-C.

Therapeutic effect develops within one week after the start of treatment with rosuvastatin. Maximum therapeutic effect is usually achieved by the 4th week of therapy and is maintained with regular use of the drug.

It is effective in adult patients with hypercholesterolemia with or without hypertriglyceridemia including patients with diabetes mellitus and familial hypercholesterolemia. Pharmacokinetics:

Absorption and distribution

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

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. Approximately 90% of rosuvastatin is bound to plasma proteins, mainly to albumin.

Metabolism

It is subject to limited metabolism (about 10%). Rosuvastatin is a non-core substrate for metabolism by cytochrome P450 isoenzymes. The main isoenzyme involved in the metabolism of rosuvastatin is CYP2C9 isoenzyme. CYP2C19 CYP3A4 and CYP2D6 isoenzymes are less involved in metabolism.

The main identified metabolites of rosuvastatin are N-desmethylrosuvastatin and lactone metabolites. N-desmethylrosuvastatin is approximately 50% less active than the original rosuvastatin lactone metabolites are pharmacologically inactive. More than 90% of the pharmacological activity for inhibition of circulating HMG-CoA reductase is provided by rosuvastatin and the rest by its metabolites.

The plasma elimination half-life (T1/2) is approximately 19 hours. The elimination half-life does not change when increasing the dose of the drug.

The geometric mean plasma clearance is approximately 50 liters/hour (coefficient of variation 217%). As with other HMG-CoA reductase inhibitors, the membrane cholesterol transporter is involved in the “hepatic” uptake of rosuvastatin and has an important role in hepatic elimination of rosuvastatin.

Linearity

The systemic exposure of rosuvastatin increases in proportion to the dose. Pharmacokinetic parameters do not change with daily administration.

Particular patient populations

Age and sex

Gender and age have no clinically significant effect on the pharmacokinetics of rosuvastatin.

Ethnic groups

Pharmacokinetic studies have shown an approximately two-fold increase in median AUC (area under the concentration-time curve) and Cmax (maximum plasma concentration) of rosuvastatin in patients of mongoloid race (Japanese Chinese, Filipino, Vietnamese and Korean) compared to Caucasians; median AUC and Cmax increased 13-fold in Indian patients. Pharmacokinetic analysis showed no clinically significant differences in the pharmacokinetics of rosuvastatin among Caucasians and blacks.

Renal failure

In patients with mild to moderately severe renal impairment, plasma concentrations of rosuvastatin or N-desmethylrosuvastatin do 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 that of N-desmethylrosuvastatin 9 times higher than in healthy volunteers. Plasma concentrations of rosuvastatin were approximately 50% higher in patients on hemodialysis than in healthy volunteers.

Hepatic failure

In patients with various stages of hepatic failure, there was no increase in the half-life of rosuvastatin in patients with a Child-Pugh score of 7 or lower. Two patients with Child-Pugh scores 8 and 9 showed at least a 2-fold increase in half-life.

There is no experience with rosuvastatin in patients with more than a Child-Pugh score of 9.

Genetic polymorphisms

HMG-CoA reductase inhibitors including rosuvastatin bind to the transport proteins OATP1B1 (organic anion transport polypeptide involved in hepatocyte capture of statins) and BCRP (efflux transporter). Carriers of SLCO1B1 (OATP1B1) p.521CC and ABCG2 (BCRP) p.421AA genotypes had 16- and 24-fold increased exposure (AUC) to rosuvastatin, respectively, compared with carriers of SLCO1B1 p.521TT and ABCG2 p.421CC genotypes.

Indications

– Primary Fredrickson hypercholesterolemia (type IIa including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb) as an adjunct to diet when diet and other nonmedicamental therapies (e.g. exercise, weight loss) are insufficient;

– familial homozygous hypercholesterolemia as an adjunct to diet and other lipid-lowering therapy (such as LDL-apheresis) or when such therapy is not sufficiently effective;

Hypertriglyceridemia (Fredrickson type IV) as an adjunct to diet;

– To slow the progression of atherosclerosis as an adjunct to diet in patients who are indicated for therapy to lower total cholesterol and LDL-C;

– primary prevention of major cardiovascular complications (stroke, arterial revascularization) in adult patients without clinical signs of CHD but with increased risk of CHD (age over 50 years for men and over 60 years for women) increased concentration of C-reactive protein (≥ 2 mg/L) in presence of at least one additional risk factor such as hypertension low concentration of HDL-C, smoking family history of early-onset CHD.

Active ingredient

Composition

One film-coated tablet, 5 mg contains:

the active substance: rosuvastatin calcium – 5.21 mg (in terms of rosuvastatin 5.0 mg);

excipients: microcrystalline cellulose – 49.19 mg, pregelatinized starch – 24.00 mg, colloidal silica (aerosil) – 0.80 mg, magnesium stearate – 0.80 mg;

Pill coating: Opadray II pink 3.20 mg (polyvinyl alcohol – 1.28 mg, titanium dioxide – 0.78 mg, macrogol (polyethylene glycol) – 0.65 mg, talc – 0.47 mg, dye carmine red (E120) – 0.02 mg).

How to take, the dosage

To the mouth, do not chew or crush the tablet, swallow it whole with water. The drug can be taken at any time of the day regardless of the time of meals.

People should start a standard hypocholesterolemic diet prior to initiating therapy with Cardiolip and continue this diet during treatment.

The dose of the drug should be adjusted individually depending on the goals of therapy and the therapeutic response to treatment, taking into account current recommendations for target lipid concentrations.

The recommended starting dose for patients starting therapy or transitioning from other HMG-CoA reductase inhibitors should be 5 or 10 mg of Cardiolip once daily.

When choosing the initial dose, individual cholesterol levels should be taken into account and the possible risk of cardiovascular complications should be taken into account as well as the potential risk of side effects. If necessary, the dose may be increased to a larger one in 4 weeks (see section “Pharmacodynamics”).

With regard to the possible development of side effects when taking a dose of 40 mg compared to lower doses of the drug (see section “Side Effects”).

Particularly in patients with severe hypercholesterolemia and high risk of cardiovascular complications (especially in patients with familial hypercholesterolemia) who have not achieved the desired therapy result with 20 mg dose and who will be under specialist supervision (see section “Special indications”), the dose increase to 40 mg after additional dosing above recommended initial dose during 4 weeks of therapy may be carried out only.) We recommend especially close monitoring of patients receiving 40 mg.

Prescribing a dose of 40 mg to patients who have not previously seen a physician is not recommended. After 2-4 weeks of therapy and/or if the dose of Cardiolip is increased, lipid metabolism should be monitored (if necessary, the dose should be adjusted).

The use of the drug in a higher dose than 40 mg is not justified due to increased side effects and in most cases is not recommended.

Elderly patients

There is no need for dose adjustment.

Patients with renal impairment

Dose adjustment is not required in patients with mild to moderate renal impairment.

In patients with severe renal impairment (CKR less than 30 ml/min), the use of Cardiolip is contraindicated.

The use of the drug in a dose of 40 mg is contraindicated in patients with moderate renal impairment (CK 30-60 mL/min) (see section “Special Precautions” “Pharmacodynamics”).

In patients with moderate renal dysfunction, a starting dose of 5 mg is recommended.

Patients with hepatic impairment

Rosuvastatin is contraindicated in patients with active liver disease (see section “Contraindications”).

Particular populations

Ethnic groups

In studying pharmacokinetic parameters of rosuvastatin in patients belonging to different ethnic groups an increase in systemic concentration of rosuvastatin among Japanese and Chinese was noted (see section “Special indications”). This fact should be considered when prescribing Cardiolip in these groups of patients.

When prescribing doses of 10 and 20 mg, the recommended starting dose for mongoloid patients is 5 mg. A dose of 40 mg is contraindicated in patients of the mongoloid race (see Contraindications).

Genetic polymorphisms

Carriers of SLCOB1 (OATP1B1) c.521CC and ABCG2 (BCRP) c.421AA had increased exposure (AUC) to rosuvastatin compared to carriers of SLCO1B1 c.52ITT and ABCG2 c.421CC genotypes.

For c.521CC or c.421AA genotype carriers, the recommended maximum dose of Cardiolip is 20 mg once daily (see Pharmacokinetics, Caution and Interaction with Other Drugs and Other Drug Interactions).

Patients with predisposition to myopathy

Patients with factors that may indicate a predisposition to myopathy are contraindicated at a dose of 40 mg (see

Contraindications). When doses of 10 and 20 mg are prescribed, the recommended starting dose for this group of patients is 5 mg (see Contraindications).

Companion therapy

Rosuvastatin binds to various transport proteins (in particular to OATP1B1 and BCRP). Co-administration of Cardiolip with drugs (such as cyclosporine, some HIV protease inhibitors including the combination of riganavir with atazanavir lopinavir and/or tipranavir) that increase plasma concentrations of rosuvastatin due to interaction with transport proteins may increase the risk of myopathy (including rhabdomyolysis) (see sections “Cautions” and “Interaction with other medicinal products and other types of drug interactions”). In such cases, the possibility of prescribing alternative therapy or temporary discontinuation of Cardiolip should be assessed. If the use of the above drugs is necessary, the benefit-risk ratio of concomitant therapy with Cardiolip should be assessed and the possibility of reducing its dose should be considered (see section “Interaction with other medicinal products and other drug interactions”).

Interaction

Influence of other drugs on rosuvastatin

Transport protein inhibitors: Rosuvastatin binds to several transport proteins, in particular to OATP1B1 and BCRP. Concomitant use of drugs that are inhibitors of these transport proteins may be accompanied by increased plasma concentrations of rosuvastatin and an increased risk of myopathy (see Table 1 and sections “Administration and Dose” and “Precautions”).

Cyclosporine: concomitant use of rosuvastatin and cyclosporine had an average AUC of 7 times higher than that observed in healthy volunteers (see Table 1). No effect on the plasma concentration of cyclosporine. Rosuvastatin is contraindicated in patients taking cyclosporine (see section “Contraindications”).

Human immunodeficiency virus (HIV) protease inhibitors: although the exact mechanism of interaction is unknown, co-administration of HIV protease inhibitors may result in a significant increase in exposure to rosuvastatin (see Table 1). A pharmacokinetic study of concomitant use of 20 mg rosuvastatin with a combination drug containing two HIV protease inhibitors (400 mg lopinavir/100 mg ritonavir) in healthy volunteers resulted in approximately two and five-fold increases in AUC(0-24) and Cmax of rosuvastatin, respectively. Therefore, concomitant administration of rosuvastatin and HIV protease inhibitors is not recommended (see Sections “Administration and Doses” “Special Precautions” Table 1).

Gemfibrozil and other hypolipidemic agents: co-administration of rosuvastatin and gemfibrozil leads to a 2-fold increase in maximal plasma concentration of rosuvastatin and AUC of rosuvastatin (see section “Special Precautions”). Based on the data on specific interactions, no pharmacokinetic significant interaction with fenofibrate is expected.

Hemfibrozil fenofibrate other fibrates and lipid-lowering doses of nicotinic acid (greater than 1 g/day) increased the risk of myopathy when used concomitantly with HMG-CoA reductase inhibitors possibly due to their potential to cause myopathy when used in monotherapy (see section “Special Indications”).

In concomitant administration of the drug with gemfibrozil with nicotinic acid in lipid-lowering doses (greater than 1 g/day), patients are recommended a starting dose of 5 mg. Taking a dose of 40 mg is contraindicated when combined with fibrates (see “Contraindications” “Dosage and administration” “Special Precautions”).

Ezetimibe: Concomitant administration of 10 mg rosuvastatin and 10 mg ezetimibe was associated with an increased AUC of rosuvastatin in patients with hypercholesterolemia (see Table 1). An increased risk of side effects due to pharmacodynamic interaction between rosuvastatin and ezetimibe cannot be excluded.

Antacids: concomitant use of rosuvastatin and suspensions of antacids containing magnesium and aluminum hydroxide leads to a decrease in plasma concentration of rosuvastatin by approximately 50%. This effect is weaker if antacids are used 2 hours after rosuvastatin administration. The clinical significance of this interaction has not been studied.

Eritromycin: Concomitant use of rosuvastatin and erythromycin decreases AUC of rosuvastatin by 20% and Cmax of rosuvastatin by 30%. This interaction may occur due to increased intestinal motility caused by taking erythromycin.

Cytochrome P450 isoenzymes: Results of in vivo and in vitro studies have shown that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. In addition, rosuvastatin is a weak substrate for these isoenzymes. Therefore, no interaction of rosuvastatin with other drugs at the level of metabolism involving cytochrome P450 is expected.

There have been no clinically significant interactions of rosuvastatin with fluconazole (inhibitor of CYP2C9 and CYP3A4 isoenzymes) and ketoconazole (inhibitor of CYP2A6 and CYP3A4 isoenzymes).

Fusidic acid: There have been no studies on interaction between rosuvastatin and fusidic acid; as with other statins, there have been post-marketing reports of rhabdomyolysis with concomitant use of rosuvastatin and fusidic acid; patients should be observed and if necessary, temporary discontinuation of rosuvastatin may be indicated.

Drug interactions that require dosage adjustment of rosuvastatin (see Table 1)

The dose of Cardiolip should be adjusted if it is necessary to co-administer with drugs that increase exposure to rosuvastatin.

The instructions for use for these drugs should be read before prescribing them concomitantly with Cardiolip.

If exposure is expected to increase 2-fold or more, the starting dose of Cardiolip should be 5 mg once daily.

The maximum daily dose of Cardiolip should also be adjusted so that the expected exposure to rosuvastatin does not exceed that of the 40 mg dose taken without concomitant administration of drugs that interact with rosuvastatin. For example, maximum daily dose of the drug Cardiolip while concomitant use with gemfibrozil is 20 mg (19-fold increase of exposure) with ritonavir/atazanavir – 10 mg (31-fold increase of exposure).

Table 1. Effect of concomitant therapy on exposure to rosuvastatin (AUC data are given in descending order) – results of published clinical trials

Cyclosporine 75 – 200 mg 2 times daily. 6 months.

10 mg once daily. 10 days

71-fold increase

Atazanavir 300 mg/ritonavir 100 mg once daily. 8 days

10 mg once

Increase 31 times

Simeprevir 152 mg once daily. 7 days

10 mg once

An increase of 28 times

Lopinavir 400 mg/ritonavir 100 mg 2 times daily. 17 days

20 mg once daily. 7 days

21-fold increase

Clopidogrel 300 mg (loading dose) then 75 mg every 24 hours

20 mg once

Increased 2-fold

Gemfibrozil 600 mg 2 times daily. 7 days

80 mg once

Increased 19-fold

Eltrombopag 75 mg once daily. 10 days

10 mg once

16-fold increase

Darunavir 600 mg/ritonavir 100 mg 2 times daily. 7 days

10 mg once daily. 7 days

15-fold increase

Tipranavir 500 mg/ritonavir 200 mg 2 times daily. 11 days

10 mg once

Increased 14 times

Dronedarone 400 mg 2 times daily.

No data

14-fold increase

/p>

Itraconazole 200 mg once daily. 5 days

10 mg or 80 mg once

Increased 14 times

Ezetimibe 10 mg once daily. 14 days

10 mg once daily. 14 days

12-fold increase

Fosamprenavir 700 mg/ritonavir 100 mg 2 times per day. 8 days

10 mg once

No change

Aleglitazar 03 mg 7 days

/p>

40 mg 7 days

No change

/p>

Silymarin 140 mg 3 times a day. 5 days

10 mg once

No change

Phenofibrate 67 mg 3 times daily.7 Days

10 mg 7 days

No change

Rifampin 450 mg once daily. 7 days

20 mg once

No change

Ketoconazole 200 mg 2 times daily. 7 days

80 mg once

No change

Fluconazole 200 mg once daily. 11 days

80 mg once

No change

Erythromycin 500 mg 4 times daily. 7 days

80 mg once

28% reduction

Baicalin 50 mg 3 times daily. 14 days

20 mg once

47% reduction

The effect of using rosuvastatin on other drugs

Vitamin K antagonists: Starting therapy with rosuvastatin or increasing the dose of the drug in patients receiving concomitant vitamin K antagonists (e.g., warfarin) may increase the International Normalized Ratio (INR). Discontinuation of rosuvastatin or reduction of the drug dose may lead to a decrease in INR. In such cases, it is recommended to monitor INR.

Peroral contraceptives/hormone replacement therapy: Concomitant use of rosuvastatin and oral contraceptives increases AUC of ethinylestradiol and AUC of nogestrel by 26% and 34%, respectively. This increase in plasma concentration should be considered when selecting a dose of oral contraceptives. There are no pharmacokinetic data on concomitant use of rosuvastatin and hormone replacement therapy, therefore a similar effect cannot be excluded when using this combination. However, this combination was widely used in clinical trials and was well tolerated by patients.

Other medicinal products: No clinically significant interaction of rosuvastatin with digoxin is expected.

Special Instructions

Renal effects

In patients receiving high doses of rosuvastatin (mostly 40 mg), there was tubular proteinuria, which in most cases was transient. This proteinuria was not indicative of acute renal disease or progression of renal disease. In patients taking the drug at a dose of 40 mg it is recommended to monitor renal function parameters during treatment.

Musculoskeletal disorders

The following musculoskeletal effects have been reported with rosuvastatin at all doses and especially with doses greater than 20 mg: myalgia myopathy in rare cases rhabdomyolysis.

Creatine phosphokinase activity determination

The determination of CPK activity should not be performed after vigorous physical activity or in the presence of other possible causes of increased CPK activity, which may lead to misinterpretation of the results. If the baseline CPK activity is significantly elevated (5 times higher than the upper limit of normal) a repeat measurement should be performed after 5-7 days.

The therapy should not be started if the repeat test confirms initial CPK activity (more than 5 times the upper limit of normal).

Pending therapy

In the administration of rosuvastatin, as with other HMG-CoA reductase inhibitors, caution should be exercised in patients with existing risk factors for myopathy/rhabdomyolysis (see section “Caution”) to consider the risk/benefit ratio of therapy and perform clinical monitoring.

In therapy

The patient should be informed to immediately inform the physician if there is a sudden onset of muscle pain, muscle weakness, or cramps especially in conjunction with malaise and fever. In such patients, CPK activity should be determined. The therapy should be stopped if CPK activity is significantly elevated (more than 5 times the upper limit of normal) or if muscle symptoms are severe and cause daily discomfort (even if CPK activity is not more than 5 times the upper limit of normal). If symptoms disappear and CPK activity returns to normal, re prescription of rosuvastatin or other HMG-CoA reductase inhibitors at lower doses with close monitoring of the patient should be considered. Routine monitoring of CPK activity in the absence of symptoms is not advisable.

There have been very rare cases of immune-mediated necrotizing myopathy with clinical manifestations as persistent proximal muscle weakness and increased serum CPK activity during treatment or upon discontinuation of statins, including rosuvastatin. Additional muscular and nervous system serologic studies and therapy with immunosuppressive agents may be required.

There have been no indications of increased skeletal muscle effects with rosuvastatin and concomitant therapy. However an increase in myositis and myopathy has been reported in patients taking other HMG-CoA reductase inhibitors in combination with fibrin acid derivatives including gemfibrozil cyclosporine nicotinic acid in lipid-lowering doses (more than 1 g/day) azole antifungal agents HIV protease inhibitors and macrolide antibiotics.

Gemfibrozil increases the risk of myopathy when coadministered with some HMG-CoA reductase inhibitors. Thus, concomitant use of rosuvastatin and gemfibrozil is not recommended.

The risk/benefit ratio of co-administration of rosuvastatin and fibrates or lipid-lowering doses of nicotinic acid should be carefully weighed. Administration of Cardiolip in dose 40 mg together with fibrates is contraindicated (see sections “Interaction with other drugs and other forms of drug interactions” “Contraindications”)

A 2-4 weeks after treatment start and/or when increasing the dose of Cardiolip is necessary to control lipid metabolism parameters (if necessary a dose adjustment is required).

The liver

Liver function tests are recommended prior to therapy and 3 months after the start of therapy. Administration of Cardiolip should be discontinued or the dose of the drug should be reduced if serum hepatic transaminase activity exceeds 3 times the upper limit of normal.

In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, therapy for underlying diseases should be performed before starting treatment with rosuvastatin.

Particular populations. Ethnic groups

Pharmacokinetic studies in Chinese and Japanese patients have shown increased systemic rosuvastatin concentrations compared to those in European patients (see sections “Administration and Doses” and “Pharmacokinetics”).

HIV protease inhibitors

The co-administration of the drug with HIV protease inhibitors is not recommended (see section “Interaction with other medicinal products and other drug interactions”).

Interstitial lung disease

Single cases of interstitial lung disease have been reported with some statins, especially over the long term. Manifestations of the disease may include dyspnea, non-productive cough, and worsening of general well-being (weakness, weight loss, and fever). If interstitial lung disease is suspected, statin therapy should be discontinued.

Type 2 diabetes mellitus

In patients with glucose concentrations between 56 and 69 mmol/L, rosuvastatin therapy has been associated with an increased risk of developing type 2 diabetes mellitus.

There have been no studies on the effect of rosuvastatin on the ability to drive vehicles and use machines. Caution should be exercised when driving motor transport or performing work requiring increased concentration and rapid psychomotor reactions (dizziness and weakness may occur during therapy).

Contraindications

For the drug in a daily dose of 5 mg 10 mg and 20 mg:

– hypersensitivity to rosuvastatin or any of the components of the drug;

– childhood age less than 18 years;

– active-phase liver disease, including persistent elevation of serum transaminase activity and any increase in serum transaminase activity (more than 3 times the upper limit of normal);

– severe renal dysfunction (CKG less than 30 ml/min);

– myopathy and predisposition to myotoxic complications;

– concomitant use of cyclosporine;

– in women: pregnancy breastfeeding period lack of adequate methods of contraception/

For the drug in a daily dose of 40 mg:

– hypersensitivity to rosuvastatin or any of the components of the drug;

– children under 18 years of age;

– concomitant administration of cyclosporine;

– in women: pregnancy breastfeeding period lack of adequate methods of contraception;

– liver disease in the active phase including persistent increase in serum transaminase activity and any increase in serum transaminase activity (more than 3 times the upper limit of normal) to patients with risk factors for myopathy/rhabdomyolysis namely:

– moderate renal insufficiency (CK less than 60 mL/min);

– hypothyroidism;

– personal or family history of muscle disease;

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

– excessive use of alcohol;

– conditions that may lead to increased plasma concentrations of rosuvastatin;

– concomitant use of fibrates;

– use in patients of mongoloid race.

For the drug in a daily dose of 5 mg 10 mg and 20 mg:

Having a risk of myopathy/rhabdomyolysis – renal insufficiency hypothyroidism personal or family history of hereditary muscle disease and prior history of muscle toxicity with other HMG-CoA reductase inhibitors (statins) or fibrates; excessive alcohol consumption; age over 65 years; conditions with increased plasma concentrations of rosuvastatin; race (mongoloid race); concomitant administration with fibrates (see section “Pharmacokinetics”). section “Pharmacokinetics”); history of liver disease; sepsis; arterial hypotension; extensive surgical interventions trauma severe metabolic endocrine or water-electrolyte disorders or uncontrolled convulsive seizures.

For a daily dose of 40 mg:

Mild renal impairment (CK more than 60 ml/min); age over 65 years; history of liver disease; sepsis; arterial hypotension; extensive surgical interventions trauma severe metabolic endocrine or water-electrolyte disorders or uncontrolled seizures.

Patients with hepatic impairment

There is no data or experience with the drug in patients with more than a Child-Pugh score of 9 (see sections “Pharmacodynamics” and “Special Precautions”).

Side effects

Side effects observed when taking Cardiolip are usually mild and go away on their own. As with other HMG-CoA reductase inhibitors, the incidence of side effects is mostly dose-dependent.

The incidence of adverse effects is presented according to the classification of the World Health Organization: Frequent (> 1/100 < 1/10); infrequent (> 1/1000 < 1/100); rare (> 1/10000 < 1/1000); very rare (< 1/10000) unspecified frequency (cannot be calculated from available data).

Immune system:

Rare: hypersensitivity reactions including angioedema

Endocrine system:

Often: type 2 diabetes mellitus

Central nervous system disorders:

Often: headache dizziness

Digestive tract:

Often: constipation nausea abdominal pain

Rarely: pancreatitis

Skin disorders:

Infrequently: skin itching rash urticaria

Musculoskeletal disorders:

Often: myalgia;

Rarely: Myopathy (including myositis) rhabdomyolysis

Other:

Often: asthenic syndrome

Urinary system disorders:

In patients receiving rosuvastatin, proteinuria may be detected. Changes in the amount of protein in the urine (from no or trace amounts to ++ or more) are observed in less than 1% of patients receiving 10-20 mg of the drug and in approximately 3% of patients receiving 40 mg of the drug.

Significant changes in the amount of protein in the urine have been noted with the 20 mg dose.

In most cases, proteinuria decreases or disappears during therapy and does not indicate acute or progressive existing renal disease.

Musculoskeletal disorders:

The following musculoskeletal effects have been reported with rosuvastatin at all doses and particularly with doses greater than 20 mg: myalgia myopathy (including myositis) in rare cases, rhabdomyolysis with or without acute renal failure.

Dose-dependent increases in creatine phosphokinase (CPK) activity have been observed in a small number of patients taking rosuvastatin. In most cases it has been mildly asymptomatic and transient. In case of increased CPK activity (more than 5 times the upper limit of normal), therapy should be suspended (see section “Special Precautions”).

Hepatic disorders:

When using rosuvastatin, a dose-dependent increase in hepatic transaminase activity is observed in a small number of patients. In most cases it is mildly asymptomatic and temporary.

Laboratory measures:

Elevated glucose concentrations bilirubin activity gamma-glutamyl transpeptidase alkaline phosphatase thyroid function abnormalities.

Postmarketing use

The following side effects have been reported in the postmarketing use of rosuvastatin:

Hematopoietic system side effects

Unspecified frequency: Thrombocytopenia

Digestive tract disorders

Very rare: jaundice hepatitis

Rarely: increased “liver” transaminase activity

Unspecified frequency: diarrhea

Musculoskeletal disorders

Very rare: arthralgia

Unspecified frequency: Immune-mediated necrotizing myopathy

Central nervous system disorders

Very rare: loss or impairment of memory; unspecified frequency: peripheral neuropathy.

Respiratory system disorders

Unspecified frequency: cough shortness of breath

Urinary system disorders

Very rare: Hematuria

Skin and subcutaneous fatty tissue disorders

Unspecified frequency: Stevens-Johnson syndrome

Reproductive and mammary system disorders

Unspecified frequency – gynecomastia

Other

Unspecified frequency: Peripheral edema

The following side effects have been reported with some statins: depression sleep disturbance including insomnia and “nightmares” dreams sexual dysfunction hyperglycemia increased concentration of glycosylated hemoglobin.

Ione cases of interstitial lung disease have been reported, especially with long-term use of the drug (see “Special Precautions”).

Overdose

The pharmacokinetic parameters of rosuvastatin do not change when several daily doses are taken simultaneously.

Symptoms: No symptoms specific to rosuvastatin have been observed. They are effects reinforced and similar to those described under “Side effects”.

Treatment: There is no specific treatment for rosuvastatin overdose or specific antidote. Timely gastric lavage and symptomatic treatment are recommended; control of liver function and CPK activity as well as measures aimed at maintenance of functions of vital organs and systems are necessary; hemodialysis is ineffective.

Pregnancy use

Cardiolip is contraindicated in pregnancy and during breastfeeding.

Women of reproductive age should use adequate methods of contraception.

Because cholesterol and other products of cholesterol biosynthesis are important for fetal development, the potential risk of HMG-CoA reductase inhibition exceeds the benefit of using the drug in pregnant women.

If pregnancy is diagnosed during therapy, the drug should be discontinued immediately.

There are no data on excretion of rosuvastatin with the breast milk; therefore, during breast-feeding the drug should be discontinued (see section “Contraindications”).

Similarities