Cardiolipus pills 5mg, 90pcs

Composition

One film-coated tablet of 5 mg contains:

Active ingredient:  rosuvastatin calcium – 5.21 mg (based on rosuvastatin 5.0 mg);

excipients:  cellulose microcrystalline – 49,19 mg, starch pregelatinization – 24,00 mg, silicon dioxide colloid (Aerosil) and 0.80 mg, magnesium stearate – 0,80 mg;

shell tablets: pink Opadry II of 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 (E 120) – 0.02 mg).

Pharmacological action

Pharmacotherapy group

Hypolipidemic agent – HMG-CoA reductase inhibitor

ATX code

C10AA

Pharmacodynamics :

Hypolipidemic drug is a selective competitive inhibitor of the HMG-CoA reductase enzyme that converts 3-hydroxy-3-methylglutarylcoa to cholesterol precursor mevalonate. The main target of rosuvastatin action is the liver, where cholesterol synthesis and catabolism of low-density lipoproteins (LDL) are carried out. Rosuvastatin increases the number of LDL receptors on the surface of liver cells, increasing the uptake and catabolism of LDL, which in turn leads to inhibition of the synthesis of very low-density lipoproteins (VLDL), thereby reducing the total amount of LDL and VLDL.

Rosuvastatin reduces elevated concentrations of LDL cholesterol (LDL-C) total cholesterol (TC) triglycerides (TG) increases the concentration of high-density lipoprotein cholesterol (HDL-LH 1 VP) and also reduces the concentration of apolipoprotein B (apoB) VLDL-C TG-VLDL and increases the concentration of apolipoprotein A-I (ApoA-I).

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

Atherogenicity index = (TC – HDL-C) / HDL-C.

The therapeutic effect develops within one week after starting treatment with rosuvastatin. The 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.

The additive effect is observed in combination with fenofibrate (in relation to the concentration of TG) and nicotinic acid in lipid-lowering doses (in relation to the concentration of HDL-C). However, the possibility of such combinations should be decided by the attending physician, taking into account the possible risks (see also the section “Special Instructions”).

Pharmacokinetics:

Absorption and distribution

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

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

Metabolism

It undergoes a 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 the CYP2C9 isoenzyme. The isoenzymes CYP2C19, CYP3A4 and CYP2D6 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 in inhibiting circulating HMG-CoA reductase is provided by rosuvastatin and the rest by its metabolites.

Deduction

Approximately 90% of the rosuvastatin dose is excreted unchanged through the intestine (including absorbed and unabsorbed rosuvastatin). The remaining part is excreted by the kidneys.

The plasma half-life (T 1/2) is approximately 19 hours. The half-life does not change with increasing dose of the drug.

The average geometric plasma clearance is approximately 50 l / h (coefficient of variation 217%). As in the case of other HMG-CoA reductase inhibitors, the process of” hepatic ” uptake of rosuvastatin involves a membrane cholesterol transporter that 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 daily use.

Special patient populations

Age and gender

Gender and age do not have a clinically significant effect on the pharmacokinetics of rosuvastatin.

Ethnic groups

Pharmacokinetic studies have shown an approximately twofold increase in the median AUC (area under the concentration-time curve) and Cmax (maximum plasma concentration) of rosuvastatin in patients of the Mongolian race (Japanese Chinese Filipinos Vietnamese and Koreans) compared with Caucasians; in Indian patients, an increase in the median AUC and Cmax by 13 times was shown. Pharmacokinetic analysis did not reveal clinically significant differences in the pharmacokinetics of rosuvastatin among Caucasians and representatives of the black race.

Kidney failure

In patients with mild to moderate renal insufficiency, the plasma concentration of rosuvastatin or N-desmethylrosuvastatin does not change significantly.

In patients with severe renal insufficiency (creatinine clearance < 30 ml/min), the concentration of rosuvastatin in blood plasma is 3 times higher and the concentration of N-desmethylrosuvastatin is 9 times higher than in healthy volunteers. The plasma concentration of rosuvastatin in hemodialysis patients was approximately 50% higher than in healthy volunteers.

Liver failure

In patients with various stages of hepatic insufficiency, there was no increase in the half-life of rosuvastatin in patients with 7 points or lower on the Child-Pugh scale. In two patients with Child-Pugh scores 8 and 9, the elimination half-life was increased at least 2-fold.

There is no experience of using rosuvastatin in patients with more than 9 points on the Child-Pugh scale.

Genetic polymorphism

HMG-CoA reductase inhibitors, including rosuvastatin, bind to the transport proteins OATP 1 In 1 (an organic anion transport polypeptide involved in the uptake of statins by hepatocytes) and BCRP (efflux transporter). Carriers of the SLCO1B1 (OATR 1V1) C. 521CC and ABCG2 (BCRP) C. 421AA genotypes showed a 16-and 24-fold increase in rosuvastatin exposure (AUC), respectively, compared to carriers of the SLCO1B1 C. 521TT and ABCG2 C. 421CC genotypes.

Indications

– Primary hypercholesterolemia according to the classification of Fredrickson (type IIA including heterozygous family hypercholesterolemia) or mixed hypercholesterolemia (type IIb) as an adjunct to diet when diet and other non-pharmacological treatments (e. g. exercise weight loss) are insufficient;

family homozygous hypercholesterolemia as an adjunct to diet and other Lipetskaya therapy (e. g. LDL-apheresis) or in cases where such therapy is not effective enough;

hypertriglyceridemia (type IV according to the classification of Fredrickson) as a Supplement to the diet;

– to slow the progression of atherosclerosis as an adjunct to diet in patients for whom therapy is shown to reduce the concentration of total cholesterol and cholesterol-LDL;

– primary prevention of major cardiovascular complications (stroke, heart attack, arterial revascularization) in adult patients without clinical signs of coronary artery disease but with an increased risk of its development (the age of 50 years for men and over 60 years for women) increased concentration of C-reactive protein (≥ 2 mg/l) in the presence of at least one additional risk factors such as hypertension low concentration of HDL-C non-Smoking family history of early coronary artery disease.

Use during pregnancy and lactation

Cardiolip is contraindicated during pregnancy and lactation.

Women of reproductive age should use 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 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 the excretion of rosuvastatin in breast milk, so the drug should be discontinued during breastfeeding (see the section “Contraindications”).

Contraindications

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

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

– children’s age up to 18 years;

– liver disease in the active phase including a persistent increase in serum transaminases and any increase of transaminases in blood serum (more than 3 times as compared with the upper limit of normal);

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

myopathy and a predisposition to the development of myotoxicity complications;

– concomitant use of cyclosporine;

– in women: pregnancy, breastfeeding, the 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;

– simultaneous use of cyclosporine;

– in women: pregnancy, breast-feeding, lack of adequate methods of contraception;

– liver diseases in the active phase, including a persistent increase in serum transaminase activity and any increase in serum transaminase activity (more than 3 timesAntacids: concomitant use of rosuvastatin and antacid suspensions containing magnesium and aluminum hydroxide leads to a decrease in the plasma concentration of rosuvastatin by approximately 50%. This effect is less pronounced if antacids are applied 2 hours after taking rosuvastatin. The clinical significance of this interaction has not been studied.

Erythromycin: concomitant use of rosuvastatin and erythromycin resulted in a 20% decrease in rosuvastatin AUC and a 30% decrease in rosuvastatin cmax. This interaction may occur as a result of increased intestinal motility caused by taking erythromycin.

Cytochrome P450 isoenzymes: 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, rosuvastatin is not expected to interact with other drugs at the metabolic level involving cytochrome P 450.

There was no clinically significant interaction of rosuvastatin with fluconazole (an inhibitor of the CYP2C9 and CYP3A4 isoenzymes) and ketoconazole (an inhibitor of the CYP2A6 and CYP3A4 isoenzymes).

Fusidic acid: studies on the interaction of rosuvastatin and fusidic acid have not been conducted; as with other statins, there have been post-marketing reports of cases of rhabdomyolysis with simultaneous use of rosuvastatin and fusidic acid; patients should be monitored and, if necessary, temporarily stop taking rosuvastatin.

Drug interactions that require dose adjustment of rosuvastatin (see table 1)

The dose of Cardiolip should be adjusted if it is necessary to use it together with drugs that increase exposure to rosuvastatin.

You should read the instructions for use of these drugs before prescribing them simultaneously with Cardiolip.

If exposure is expected to increase by a factor of 2 or more, the initial dose of Cardiolip should be 5 mg once a day.

It is also necessary to adjust the maximum daily dose of Cardiolip so that the expected exposure to rosuvastatin does not exceed that for a dose of 40 mg taken without simultaneous use of drugs interacting with rosuvastatin. For example, the maximum daily dose of Cardiolip when used concomitantly with gemfibrozil is 20 mg (19-fold increase in exposure) with ritonavir/atazanavir-10 mg (31-fold increase in exposure).

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

of Cyclosporine 75-200 mg 2 times a day. 6 months.	10 mg once a day for 10 days	71x increase
Atazanavir 300 mg / ritonavir 100 mg once daily for 8 days	10 mg once	31x increase
Simeprevir 152 mg once a day for 7 days	10 mg once	28x magnification
Lopinavir 400 mg / ritonavir 100 mg twice daily for 17 days	20 mg once daily for 7 days	21x increase
Clopidogrel 300 mg (loading dose) then 75 mg after 24 hours	20 mg once	2-fold increase
Gemfibrozil 600 mg 2 times daily for 7 days	80 mg once	19x increase
Eltrombopag 75 mg once a day for 10 days	10 mg once	16x magnification
Darunavir 600 mg / ritonavir 100 mg twice daily for 7 days	10 mg once daily for 7 days	15x magnification
Tipranavir 500 mg / ritonavir 200 mg twice daily for 11 days	10 mg once	14x magnification
Dronedarone 400 mg 2 times a day.	No data available	14x magnification
Itraconazole 200 mg once a day for 5 days	10 mg or 80 mg once	14x magnification
Ezetimibe 10 mg once daily for 14 days	10 mg once daily for 14 days	12x magnification
Fosamprenavir 700 mg / ritonavir 100 mg 2 times a day for 8 days	10 mg once	No changes
Aleglitazar 03 mg 7 days	40 mg 7 days	No changes
Silymarin 140 mg 3 times a day for 5 days	10 mg once	No changes
Fenofibrate 67 mg 3 times a day 7 days	10 mg 7 days	No changes
Rifampin 450 mg once a day for 7 days	20 mg once	No changes
Ketoconazole 200 mg 2 times a day for 7 days	80 mg once	No changes
Fluconazole 200 mg once a day for 11 days	80 mg once	No changes
Erythromycin 500 mg 4 times a day for 7 days	80 mg once	28% reduction
Baikalin 50 mg 3 times a day for 14 days	20 mg once	47% reduction

Effect of rosuvastatin on other medications

Vitamin K antagonists: starting rosuvastatin therapy or increasing the dose of the drug in patients receiving concomitant vitamin K antagonists (for example, warfarin) It can lead to an increase in the International Normalized Ratio (INR). Discontinuation of rosuvastatin or a reduction in the dose of the drug may lead to a decrease in INR. In such cases, monitoring of INR is recommended.

Oral contraceptives/Hormone replacement therapy: concomitant use of rosuvastatin and oral contraceptives increases the AUC of ethinyl estradiol and AUC of norgestrel by 26% and 34%, respectively. Such an increase in plasma concentration should be taken into account when selecting the dose of oral contraceptives. There are no pharmacokinetic data on the concomitant use of rosuvastatin and hormone replacement therapy, so it is impossible to exclude a similar effect when using this combination. However, this combination was widely used during clinical trials and was well tolerated by patients.

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

How to take it, course of use and dosage

Inside do not chew or crush the tablet swallow whole with water. The drug can be prescribed at any time of the day, regardless of the time of eating.

Before starting therapy with Cardiolip, the patient should start following a standard hypocholesterolemic diet and continue to follow it during treatment.

The dose of the drug should be selected 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 to take the drug or for patients transferred from taking other HMG-CoA reductase inhibitors should be 5 or 10 mg of Cardiolip 1 time per day.

When choosing the initial dose, you should be guided by the individual cholesterol content and take into account the possible risk of cardiovascular complications, as well as the potential risk of side effects. If necessary, the dose can be increased to a larger one after 4 weeks (see the section “Pharmacodynamics”).

Due to the possible development of side effects when taking a dose of 40 mg compared to lower doses of the drug (seesection “Side effects”) increasing the dose to 40 mg after an additional dose above the recommended starting dose for 4 weeks of therapy can only be performed in patients with severe hypercholesterolemia and at high risk of cardiovascular complications (especially in patients with familial hypercholesterolemia) patients who did not achieve the desired result of therapy when taking a dose of 20 mg and who will be under the supervision of a specialist (see the section “Special instructions”). Especially careful monitoring of patients receiving the drug at a dose of 40 mg is recommended.

It is not recommended to prescribe a dose of 40 mg to patients who have not previously consulted a doctor. After 2-4 weeks of therapy and/or with an increase in the dose of Cardiolip, monitoring of lipid metabolism parameters is necessary (if necessary, dose adjustment is required).

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

No dose adjustment is required.

Patients with renal insufficiency

No dose adjustment is required in patients with mild or moderate renal insufficiency.

Cardiolip is contraindicated in patients with severe renal insufficiency (creatinine clearance < 30 ml / min).

It is contraindicated to use the drug at a dose of 40 mg in patients with moderate renal impairment (creatinine clearance 30-60 ml / min) (see the section” Special instructions “”Pharmacodynamics”).

In patients with moderate renal impairment, an initial dose of 5 mg is recommended.

Patients with hepatic insufficiency

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

Special populations

Ethnic groups

When studying the pharmacokinetic parameters of rosuvastatin in patients belonging to different ethnic groups, an increase in the systemic concentration of rosuvastatin among Japanese and Chinese was noted (see the section “Special instructions”). This fact should be taken into account when prescribing Cardiolip to these groups of patients.

When prescribing doses of 10 and 20 mg, the recommended starting dose for patients of the Mongolian race is 5 mg. It is contraindicated to prescribe the drug at a dose of 40 mg to patients of the Mongolian race (see the section “Contraindications”).

Genetic polymorphism

Carriers of the SLCOB1 (OATR 1V1) c. 521 CC and ABCG2 (BCRP) c. 421 AA genotypes showed increased exposure (AUC) to rosuvastatin compared to carriers of the SLCO1B1 c. 52ITT and ABCG2 c. 421 CC genotypes.

For patients with genotypes c. 521 CC or c. 421 AA, the recommended maximum dose of Cardiolip is 20 mg once a day (see sections “Pharmacokinetics”, ” Special instructions “and”Interaction with other drugs and other types of drug interactions”).

Patients predisposed to myopathy

It is contraindicated to prescribe the drug at a dose of 40 mg to patients with factors that may indicate a predisposition to the development of myopathy (see the section

“Contraindications”). When prescribing doses of 10 and 20 mg, the recommended initial dose for this group of patients is 5 mg (See the section “Contraindications”).

Concomitant therapy

Rosuvastatin binds to various transport proteins (in particular, OATP1 In 1 and BCRP). When Cardiolip is co-administered with medicinal products (such as cyclosporine, some HIV protease inhibitors including the combination of rigonavir with atazanavir lopinavir and / or tipranavir) that increase the concentration of rosuvastatin in plasma due to interaction with transport proteins, the risk of myopathy (including rhabdomyolysis) may increase (see sections “Special instructions” and “Interaction with other drugs and other types of drug interactions”). In such cases, the possibility of alternative therapy or temporary discontinuation of Cardiolip should be evaluated. If the use of the above drugs is necessary, the benefit-risk ratio of concomitant therapy with Cardiolip should be evaluated and the possibility of reducing its dose should be considered (see the section “Interaction with other drugs and other types of drug interactions”).

Overdose

With simultaneous use of several daily doses, the pharmacokinetic parameters of rosuvastatin do not change.

Symptoms: rosuvastatin-specific symptoms are not observed. They are enhanced effects and similar to those described in the “Side Effects”section.

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

Special instructions

Renal effects

Patients receiving high doses of rosuvastatin (mainly 40 mg) experienced tubular proteinuria, which in most cases was transient. Such proteinuria was not indicative of acute kidney disease or progressive kidney disease. In patients taking the drug at a dose of 40 mg, it is recommended to monitor the indicators of renal function during treatment.

From the musculoskeletal system

The following effects on the musculoskeletal system have been reported when rosuvastatin is used in all doses, and especially when taking doses of the drug exceeding 20 mg: myalgia, myopathy, in rare cases, rhabdomyolysis.

Determination of creatine phosphokinase activity

Determination of CKD activity should not be performed after intense physical exertion or in the presence of other possible causes of increased CKD activity, which may lead to misinterpretation of the results. If the initial CPK activity is significantly increased (5 times higher than the upper limit of normal), a second measurement should be performed after 5-7 days.

You should not start therapy if a repeated test confirms the initial CPK activity (more than 5 times higher than the upper limit of normal).

Before starting therapy

When prescribing rosuvastatin, as well as when prescribing other HMG-CoA reductase inhibitors, caution should be exercised in patients with existing risk factors for myopathy/rhabdomyolysis (see the section “With caution”), the risk-benefit ratio of therapy should be considered and clinical monitoring should be carried out.

During therapy

The patient should be informed of the need to immediately inform the doctor about cases of unexpected occurrence of muscle pain, muscle weakness or spasms, especially in combination with malaise and fever. In such patients, CPK activity should be determined. Therapy should be discontinued if CKD activity is significantly increased (more than 5 times higher than the upper limit of normal) or if muscle symptoms are severe and cause daily discomfort (even if CKD activity is increased no more than 5 times higher than the upper limit of normal). If symptoms disappear and CPK activity returns to normal, consideration should be given to re-prescribing rosuvastatin or other HMG-CoA reductase inhibitors in lower doses, with careful monitoring of the patient. Routine monitoring of CPK activity in the absence of symptoms is impractical.

Very rare cases of immuno-mediated necrotizing myopathy with clinical manifestations in the form of persistent weakness of the proximal muscles and increased CPK activity in the blood serum have been noted during treatment or upon discontinuation of statins, including rosuvastatin. Additional studies of the muscular and nervous system, serological studies, and immunosuppressive therapy may be required.

There were no signs of increased effects on skeletal muscle with rosuvastatin and concomitant therapy. However, an increase in the incidence of myositis and myopathy has been reported in patients taking other HMG-CoA reductase inhibitors in combination with fibrinic 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 co-administered with certain HMG-CoA reductase inhibitors. Therefore, concomitant use of rosuvastatin and gemfibrozil is not recommended.

The risk-benefit ratio of rosuvastatin and fibrates or lipid-lowering doses of nicotinic acid should be carefully weighed. It is contraindicated to take Cardiolip at a dose of 40 mg together with fibrates (see the sections “Interaction with other drugs and other forms of drug interaction” and “Contraindications”).

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

The liver

It is recommended to determine liver function indicators before the start of therapy and 3 months after the start of therapy. Cardiolip should be discontinued or the dose of the drug should be reduced if the activity of “hepatic” transaminases in the blood serum is 3 times higher than the upper limit of normal.

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

Special populations. Ethnic groups

In the course of pharmacokinetic studies among Chinese and Japanese patients, an increase in the systemic concentration of rosuvastatin was noted in comparison with the indicators obtained among Caucasian patients (see fig.sections “Dosage and use” and “Pharmacokinetics”).

HIV protease inhibitors

Concomitant use of the drug with HIV protease inhibitors is not recommended (“see the section” Interaction with other drugs and other types of interaction”).

Interstitial lung disease

Isolated cases of interstitial lung disease have been reported with the use of certain statins, especially for a long time. Symptoms of the disease may include shortness of breath, an unproductive cough, and poor overall health (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 was associated with an increased risk of developing type 2 diabetes.

Influence on the ability to drive vehicles and mechanisms:

No studies have been conducted to study the effect of rosuvastatin on the ability to drive a vehicle and use mechanisms. Caution should be exercised when driving vehicles or working at work that requires increased concentration of attention and speed of psychomotor reactions (dizziness and weakness may occur during therapy).

Storage conditions

At a temperature not exceeding 25 °C in the original packaging.

Keep out of reach of children.

Shelf

life is 3 years.

Do not use after the expiration date indicated on the package.

Active ingredient

Rosuvastatin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets