Cardiolip, 5 mg 60 pcs

Cardiolip is a hypolipidemic drug, a selective competitive HMG-CoA reductase inhibitor. It is effective in adult patients with hypercholesterolemia, with or without hypertriglyceridemia (regardless of race, sex or age), including patients with diabetes and familial hypercholesterolemia.

Additive effect is noted in combination with fenofibrate (with respect to reduction of TG concentration) and nicotinic acid in lipid-lowering doses (with respect to reduction of HDL-C concentration).

Indications

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

– Familial homozygous hypercholesterolemia as an adjunct to diet and other lipid-lowering therapy (e.g., LDL-apheresis), or when such therapy is not sufficiently effective.

– Hypertriglyceridemia (type IV according to Fredricksen) as an adjunct to diet.

– For slowing the progression of atherosclerosis as an adjunct to the diet in patients who are indicated for therapy to reduce the concentration of total cholesterol and LDL-C.

. – Primary prevention of major cardiovascular complications (stroke, myocardial infarction, arterial revascularization) in adult patients without clinical signs of CHD, but with an increased risk of its development (age over 50 years for men and over 60 years for women, elevated concentration of C-reactive protein (more than 2 mg/l) in the 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 contains:

the active ingredient:

rosuvastatin calcium in terms of rosuvastatin 5.00 mg;

excipients:

Microcrystalline cellulose,

Pregelatinized starch,

colloidal silicon dioxide (aerosil),

magnesium stearate;

pill coating:

opadray II pink (polyvinyl alcohol, titanium dioxide, macrogol (polyethylene glycol), talc, carmine red dye (E120)).

How to take, the dosage

The drug is taken orally. The tablet should not be chewed or crushed, swallowed whole with plenty of water, it can be taken at any time of the day, regardless of meals. If it is necessary to take the drug in a dose of 5 mg, the tablet with a dose of 10 mg should be divided.

Before initiating therapy with Cardiolip, the patient should start a standard hypocholesterolemic diet and continue to follow it 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 levels.

The recommended starting dose for patients starting to take the drug or for patients transferred from other HMG-CoA reductase inhibitors should be 5 mg (1/2 tablet of 10 mg) or 10 mg of the drug once daily.

When taking Cardiolip concomitantly with gemfibrozil, fibrates, nicotinic acid at a dose greater than 1 g/day, the recommended starting dose of the drug is 5 mg (1/2 tablet of 10 mg).

When choosing the starting dose, individual cholesterol levels should be guided by the possible risk of cardiovascular complications and the potential risk of side effects should be assessed. If necessary, the dose may be increased to a higher dose after 4 weeks.

. Because of the possible development of side effects when taking a dose of 40 mg, compared with lower doses of the drug, increasing the dose to 40 mg, after an additional dose above the recommended initial dose for 4 weeks of therapy, may only be undertaken in patients with severe hypercholesterolemia and with a high risk of cardiovascular complications (especially in patients with familial hypercholesterolemia), in whom the desired therapy outcome was not achieved when taking the 20 mg dose and who will be under medical supervision. We recommend particularly close monitoring of patients receiving the drug at a dose of 40 mg.

The 40 mg dose is not recommended in patients who have not previously seen a physician. After 2-4 weeks of therapy and/or when increasing the dose of the drug, monitoring of lipid metabolism parameters is necessary (dosage adjustment is required if necessary).

Elderly patients: No dose adjustment is required.

In patients with mild to moderate renal insufficiency, no dose adjustment is required. All doses of the drug are contraindicated in patients with severe renal failure (CKR less than 30 ml/min). The use of the drug in dose 40 mg is contraindicated in patients with moderate renal impairment (CKD less than 60 ml/min). In patients with moderate renal dysfunction, a starting dose of the drug of 5 mg (1/2 tablet of 10 mg) is recommended.

Patients with hepatic impairment: Rosuvastatin is contraindicated in patients with active liver disease. There is no experience of using the drug in patients with hepatic impairment above 9 on the Child-Pugh scale.

Particular populations

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. This fact should be considered when using Rosuvastatin in this group of patients. When using 10 mg and 20 mg doses the recommended initial dose for Asian race patients is 5 mg (1/2 tablet of 10 mg). The use of the drug in a dose of 40 mg is contraindicated in patients of Asian race.

Patients with predisposition to myopathy

The use of the drug in dose 40 mg is contraindicated in patients with factors indicating predisposition to myopathy. When using doses of 10 mg and 20 mg, the recommended starting dose for this group of patients is 5 mg (1/2 tablet of 10 mg).

When used with gemfibrozil, the drug dose should not exceed 10 mg/day.

Interaction

Cyclosporine: in concomitant use of Cardiolip and cyclosporine the AUC of rosuvastatin is on average 7 times higher than the value observed in healthy volunteers. Co-administration with rosuvastatin leads to an 11-fold increase in plasma Cmax. Does not affect the plasma concentration of cyclosporine.

Vitamin K antagonists: initiation of therapy with rosuvastatin or increasing the dose of the drug in patients receiving simultaneously vitamin K antagonists (e.g., warfarin) may lead to increased prothrombin time (International Normalized Ratio – INR). Discontinuation of rosuvastatin or reduction of the drug dose may lead to a decrease of INR (INR control is recommended).

Hemfibrozil and other hypolipidemic agents: co-administration of rosuvastatin and hemfibrozil leads to a 2-fold increase in Cmax and AUC of rosuvastatin. Based on the data on specific interaction, no pharmacokinetic interaction with fenofibrates is expected, pharmacodynamic interaction is possible.

Hemfibrozil, fenofibrate, other fibrates, and lipid-lowering doses of nicotinic acid (high doses or equivalent to 1 g per day) increase the risk of myopathy when used concomitantly with HMG-CoA reductase inhibitors, possibly due to the fact that they can also cause myopathy when used in monotherapy. When concomitant use of the drug with gemfibrozil, fibrates, nicotinic acid at a dose of more than 1 g/day, patients are recommended the initial dose of the drug 5 mg (1/2 tablet of 10 mg).

Ezetimibe: Concomitant use of rosuvastatin and ezetimibe was not accompanied by changes in AUC and Cmax of both drugs.

HIV protease inhibitors: although the exact mechanism of interaction is unknown, co-administration of HIV protease inhibitors may result in a significant increase in rosuvastatin exposure. Therefore, concomitant administration of rosuvastatin and HIV protease inhibitors during treatment of patients with human immunodeficiency virus (HIV) is not recommended.

Antacids: concomitant use of rosuvastatin and suspensions of antacids containing aluminum and magnesium hydroxide leads to a decrease in plasma concentration of rosuvastatin by about 50%. This effect is weaker if antacids are used 2 hours after taking rosuvastatin. 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 by 30%. This interaction may occur due to increased intestinal motility caused by taking erythromycin.

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 with this combination.

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

Cytochrome P450: 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 non-core substrate for these isoenzymes. No clinically significant interaction between rosuvastatin and fluconazole and ketoconazole has been observed. Co-administration of rosuvastatin and itraconazole increases the AUC of rosuvastatin by 28% (clinically insignificant). Thus, no interaction associated with metabolism through the cytochrome P450 system is expected.

Special Instructions

Before the start of therapy and during the entire period of treatment, a standard hypolipidemic diet should be followed. During treatment every 2-4 weeks lipid profile should be monitored and according to it the drug dose should be adjusted if necessary.

When using rosuvastatin in all doses, and especially in doses greater than 20 mg, transient proteinuria may be observed. In patients taking the drug in a dose of 40 mg, it is recommended to monitor renal function parameters.

Patients taking rosuvastatin in doses greater than 20 mg may experience myalgia, myopathy and, rarely, rhabdomyolysis. The determination of CPK activity should not be performed after intense physical activity or in the presence of other possible causes of CPK increase, which may lead to misinterpretation of the results. If CPK increase is 5 times higher than the upper limit of normal, a repeat measurement should be performed in 5-7 days. Therapy should not be initiated if the repeat test confirms an initial increase in CPK activity of more than 5 times the upper limit of normal.

In patients at risk of myopathy/rhabdomyolysis, the risk/benefit ratio of therapy should be considered and clinical monitoring should be performed throughout the course of treatment.

Patients should be informed to immediately inform their physician if muscle pain, muscle weakness, or cramps occur unexpectedly, especially in conjunction with malaise and fever. In such patients, CPK activity should be monitored. Therapy should be stopped if CPK activity is increased more than 5 times the upper limit of normal, or if muscle symptoms are severe and cause daily discomfort (even if CPK activity is 5 times less than the upper limit of normal). If symptoms disappear and CPK activity returns to normal, re-administration of the drug or other HMG-CoA reductase inhibitors at lower doses under close medical supervision should be considered. Routine CPK monitoring in the absence of symptoms of rhabdomyolysis is unnecessary.

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, lipid-lowering nicotinic acid, azole antifungals, HIV protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when combined 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 nicotinic acid in lipid-lowering doses should be carefully weighed.

Liver function tests are recommended before therapy and 3 months after the start of therapy. If serum ‘hepatic’ transaminase activity exceeds 3 times the upper limit of normal, the dose of the drug should be reduced or discontinued.

If hypercholesterolemia and hypothyroidism or nephrotic syndrome are combined, therapy of underlying diseases should be carried out before starting treatment with rosuvastatin.

An increase in plasma concentrations of rosuvastatin has been observed in patients of Asian race compared to patients of Caucasoid race.

In patients with blood glucose concentrations between 5.6 and 6.9 mmol/L, rosuvastatin therapy was associated with an increased risk of developing type 2 diabetes.

Women of reproductive age should use adequate methods of contraception.

Dizziness and weakness may occur during treatment, so caution should be exercised when driving vehicles and engaging in other potentially dangerous activities requiring increased concentration and rapid psychomotor reactions.

Contraindications

With caution:

Having a risk of myopathy/rhabdomyolysis – renal failure, hypothyroidism, personal or family history of hereditary muscle disease and prior history of muscle toxicity with other HMG-CoA reductase inhibitors or fibrates; alcohol dependence; age over 65 years; conditions with increased plasma concentrations of rosuvastatin; race (Asian race – Japanese and Chinese); concomitant use with fibrates; history of liver disease; sepsis; arterial hypotension; major surgery, trauma, severe metabolic, endocrine or electrolyte disorders or uncontrolled seizures.

Patients with hepatic impairment: There is no data or experience with the drug in patients with a Child-Pugh score greater than 9.

Pregnancy and lactation: Rosuvastatin is contraindicated in pregnancy and lactation. Since cholesterol and substances synthesized from cholesterol are important for fetal development, the potential risk of HMG-CoA reductase inhibition exceeds the benefits of using the drug in pregnancy.

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

Women of reproductive age should use adequate contraceptive methods.

Side effects

The central nervous system: often – headache, dizziness, asthenic syndrome; very rarely – polyneuropathy, memory loss.

The digestive system: often – constipation, nausea, abdominal pain; rarely – pancreatitis; very rare – jaundice, hepatitis; unspecified frequency – diarrhea.

Respiratory system: unspecified frequency – cough, shortness of breath.

Musculoskeletal system: common – myalgia; rare – myopathy (including myositis), rhabdomyolysis with or without acute renal failure; very rare – arthralgia.

Urinary system disorders: proteinuria (less than 1% of cases for 10 mg and 20 mg doses, 3% of cases for 40 mg doses); unspecified frequency – peripheral edema; very rare – hematuria.

Endocrine system disorders: type 2 diabetes mellitus.

Allergic reactions: rare – hypersensitivity reactions, including angioedema; infrequent – skin itching, rash, urticaria; unspecified frequency – Stevens-Johnson syndrome.

Laboratory indices: Transient dose-dependent increase in creatine phosphokinase (CPK) activity (if CPK activity increases more than 5 times the upper limit of normal, therapy should be temporarily suspended); reversible transient dose-dependent increase in ‘hepatic’ transaminases; increase in glucose concentration, bilirubin, gamma-glutamyl transpeptidase activity, alkaline phosphatase, changes in thyroid hormone levels.

With the use of some HMG-CoA reductase inhibitors (statins) the following side effects have been reported: depression, sleep disorders, including insomnia and ‘nightmares’ dreams, sexual dysfunction. Single cases of interstitial lung disease have been reported, especially with long-term use of the drugs.

The pharmacokinetic parameters of rosuvastatin do not change when multiple daily doses are administered simultaneously. Treatment of overdose is symptomatic, control of liver function and CPK activity is necessary; there is no specific antidote, hemodialysis is ineffective.

Similarities