Rosuvastatin pills 40mg 30pcs

Composition

Rosuvastatin 40 mg

Pharmacological action

Pharmaceutical group:

hypolipidemic agent-HMG-CoA reductase inhibitor.

Pharmaceutical action:

Hypolipidemic drug, a selective competitive inhibitor of HMG-CoA reductase, which converts 3-hydroxy-3-methylglutarylcoa to mevalonate, a cholesterol precursor.

The main target of action is the liver, where cholesterol synthesis and LDL catabolism are carried out. Inhibits the activity of HMG-CoA reductase (90% of the drug circulates in the blood).

Increases the number of LDL receptors on the surface of hepatocytes, increasing the uptake and catabolism of LDL, which leads to inhibition of VLDL synthesis, reducing the total amount of LDL and VLDL.

Reduces the concentration of LDL cholesterol, non-HDL cholesterol, VLDL cholesterol, total cholesterol, TG, TG-VLDL, apolipoprotein B (apoB), the ratio of LDL-cholesterol/HDL-cholesterol, total cholesterol/HDL-cholesterol, cholesterol-non-HDL/HDL-cholesterol, apoB/ApoA-I, increases the concentration of cholesterol-HDL, ApoA-I. The hypolipidemic effect is directly proportional to the prescribed dose.

The therapeutic effect appears within 1 week after the start of therapy, after 2 weeks it reaches 90% of the maximum, the maximum effect is usually achieved by 4 weeks and then remains constant.

It is effective in adult patients with hypercholesterolemia with or without hypertriglyceridemia (regardless of race, gender, or age), including those with diabetes mellitus and familial hypercholesterolemia.

The additive effect is observed in combination with fenofibrate (with respect to reducing the concentration of TG) and nicotinic acid (with respect to reducing the concentration of HDL cholesterol).

Pharmacokinetics:  

Bioavailability – 20%. Food reduces the rate of absorption. Binding to plasma proteins (mainly albumin) is 90%. TCmax – 3-5 hours. Penetrates the placental barrier. It accumulates in the liver. The volume of distribution is 134 liters.

It is metabolized in the liver by 10% of the administered dose. As with other HMG-CoA reductase inhibitors, a specific membrane transporter of cholesterol is involved in the hepatic uptake of the drug, which plays an important role in its hepatic elimination. Rosuvastatin has been shown to be a non-core substrate for metabolism by cytochrome P450 enzymes.

The main isoenzyme involved in rosuvastatin metabolism is CYP2C9. The enzymes CYP2C19, CYP3A4, and CYP2D6 are less involved in metabolism. The main metabolite is N-desmethyl, which has 1/6-1/2 the activity of rosuvastatin; lactone metabolites are pharmacologically inactive. T 1/2-19 h (does not change with increasing dose of the drug). The average geometric plasma clearance is 50 l/h.

It is mainly excreted unchanged (90%) in faeces (including adsorbed and non-adsorbed rosuvastatin); the remaining part is excreted in the urine. It is not excreted by hemodialysis.

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

Pharmacokinetic parameters depend on race: AUC in Japanese and Chinese is 2 times higher than that in residents of Europe and North America.

In patients with mild to moderate renal insufficiency, the plasma concentration of rosuvastatin or N-dismethyl does not change significantly. In patients with severe renal insufficiency (CC The plasma concentration of rosuvastatin in patients undergoing hemodialysis is approximately 50% higher than in healthy volunteers.

In patients with various stages of hepatic insufficiency with a Child-Pugh score of 7 or lower, there was no increase in rosuvastatin T1/2; in 2 patients with Child-Pugh scores of 8 and 9, a 2-fold prolongation of T1/2 was noted. There is no experience of using the drug in patients with more severe hepatic impairment.

Indications

• Primary hypercholesterolemia (type IIa, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb) as a dietary supplement when diet and other non-drug treatments (exercise, weight loss) are insufficient.
• Familial homozygous hypercholesterolemia as a dietary supplement, etc. cholesterol-lowering therapy (LDL apheresis) or in cases where such therapy is not suitable for the patient.

Contraindications

• Hypersensitivity.
• Liver diseases in the active phase (including a persistent increase in the activity of” hepatic “transaminases, as well as any increase in the activity of” hepatic ” transaminases in blood serum by more than 3 times compared to the upper limit of normal).
• Severe renal dysfunction (CKD, pregnancy, lactation; women of reproductive age who do not use adequate methods of contraception.
• Age up to 18 years (efficacy and safety have not been established).

With caution:

• Kidney failure,
• Hypothyroidism.
• Personal or family history of inherited muscle diseases and previous history of muscle toxicity when using other HMG-CoA reductase inhibitors or fibrates).
• Alcohol addiction.
• Over 65 years of age.
• A history of liver disease.
• Sepsis.
• Arterial hypotension,
• Extensive surgical interventions.
• Injuries.
• Severe metabolic, endocrine, or electrolyte disorders.
• Proteinuria.
• Uncontrolled epilepsy,
• Asians (Japanese and Chinese).

Side effects

The frequency of side effects is dose-dependent: often (1-10%), less often (0.1-1%), rarely (0.01-0.1%).

Nervous system disorders: often – headache, dizziness, asthenic syndrome; less often-anxiety, depression, insomnia, neuralgia, paresthesia.

From the gastrointestinal tract: often-constipation, nausea, abdominal pain; frequency unknown-reversible transient dose-dependent increase in the activity of “hepatic” transaminases; less often-dyspepsia (including diarrhea, flatulence, vomiting), gastritis, gastroenteritis.

From the respiratory system: often-pharyngitis; less often-rhinitis, sinusitis, bronchial asthma, bronchitis, cough, shortness of breath, pneumonia.

From the heart rate: less often-angina pectoris, increased blood pressure, palpitations, vasodilation.

From the musculoskeletal system: often-myalgia; less often-arthralgia, arthritis, muscle hypertonus, back pain, pathological fracture of the limb (without damage); rarely-myopathy, rhabdomyolysis (simultaneously with impaired renal function, while taking the drug at a dose of 40 mg).

From the urinary system: tubular proteinuria (in less than 1% of cases – for doses of 10 and 20 mg,3% of cases – for a dose of 40 mg); less often – peripheral edema (hands, feet, ankles, shins), pain in the lower abdomen, urinary tract infections.

Allergic reactions: less often – skin rash, pruritus; rarely-angioedema.

From the side of laboratory parameters: transient dose-dependent increase in CKD activity (if CKD activity increases by more than 5 times compared to the upper limit of normal, therapy should be temporarily suspended).

Other: less common-accidental injury, anemia, chest pain, diabetes mellitus, ecchymosis, flu-like syndrome, periodontal abscess.

Interaction

It does not affect the plasma concentration of cyclosporine. Cyclosporine enhances the effect of rosuvastatin (slows its excretion, increases AUC by 7 times, Cmax-by 11 times), vitamin K antagonists (including warfarin, may lead to an increase in prothrombin time, its monitoring is recommended).

Gemfibrozil enhances the effect of rosuvastatin (increases its Cmax and AUC by 2 times).

Antacids containing Al3+ and Mg2+lead to a decrease in the plasma concentration of rosuvastatin by about 50% (antacids should be used 2 hours after taking rosuvastatin, the clinical significance of such an interaction has not been studied).

Erythromycin enhances gastrointestinal motility, which leads to a decrease in the effect of rosuvastatin (reduces its AUC by 20% and Cmax by 30%).

Increases the effect of oral contraceptives (increases the AUC of ethinyl estradiol and norgestrelan by 26% and 34%, respectively, which should be taken into account when selecting the dose of oral contraceptives). Pharmacokinetic data on the simultaneous use of rosuvastatin and hormone replacement therapy are not available, therefore, a similar effect cannot be excluded when using this combination.

No clinically significant interaction of rosuvastatin with digoxin or fenofibrate is expected.

Gemfibrozil, other fibrates and lipid-lowering doses of nicotinic acid (high doses or equivalent to 1 g / day) increase the risk of myopathy when used concomitantly with other HMG-CoA reductase inhibitors, possibly due to the fact that they themselves can cause myopathy when used as monotherapy.

The results of in vivo and in vitro studies showed that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 enzymes.

In addition, rosuvastatin is a non-core substrate for these enzymes. There was no clinically significant interaction between rosuvastatin and fluconazole (a CYP2C9 and CYP3A4 inhibitor) and ketoconazole (a CYP2A6 and CYP3A4 inhibitor).

Co-administration of rosuvastatin and itraconazole (a CYP3A4 inhibitor)increases the AUC of rosuvastatin by 28% (clinically insignificant). Thus, no interaction associated with metabolism by the cytochrome P450 system is expected.

Concomitant use with drugs that reduce the concentration of endogenous steroid hormones (incl.cimetidine, ketoconazole, spironolactone), increases the risk of a decrease in endogenous steroid hormones.

How to take, course of use and dosage

Inside, the tablet should not be chewed or crushed, swallowed whole, washed down with water, it can be taken at any time of the day, regardless of food intake.

The recommended initial dose of 10 mg 1 time per day; if necessary, the dose may be increased to 20 mg after 4 weeks; increase dose to 40 mg is possible only under medical supervision in patients with severe homozygous familial hypercholesterolemia with high risk of cardiovascular complications (especially in patients with familial hypercholesterolemia) who have not achieved the desired outcome of treatment in the dose of 20 mg.

In patients with risk factors for developing myopathy, the initial dose of the drug should be 5 mg.

When administered with gemfibrazil, the rosuvastatin dose should not exceed 10 mg / day.

In patients with mild or moderate renal insufficiency, as well as in elderly adults, no dose adjustment is required. There is no experience of using the drug in patients with hepatic insufficiency above 9 on the Child-Pugh scale.

Overdose

Treatment: symptomatic, monitoring of liver function and CKD activity is necessary; there is no specific antidote, and hemodialysis is ineffective.

Special instructions

Before starting therapy and throughout the entire treatment period, a standard lipid-lowering diet should be observed. During treatment, the lipid profile should be monitored every 2-4 weeks and the dose adjusted accordingly, if necessary.

Doses of 40 mg are contraindicated in patients with risk factors for rhabdomyolysis (moderate renal failure (creatinine clearance less than 60 ml / min), hypothyroidism, own or family history of muscle diseases, myotoxicity against the background of taking other HMG-CoA reductase inhibitors or fibrates, alcohol abuse; conditions accompanied by an increase in the concentration of the drug in the systemic circulation), simultaneous intake of fibrates, Asian patients). In patients taking the drug at a dose of 40 mg, it is recommended to monitor the indicators of renal function.

Determination of CPK activity should not be performed after intense physical exertion or in the presence of other factors. possible reasons for the increase in CPK, which may lead to a misinterpretation of the results obtained. If the initial CPK is 5 times higher than the upper limit of normal, a second measurement should be performed after 5-7 days. Do not start therapy if a repeated test confirms the initial increased activity of CPK by more than 5 times compared to the upper limit of normal. In patients with existing risk factors for rhabdomyolysis, the risk-benefit ratio of therapy should be considered and clinical monitoring should be carried out throughout the course of treatment.

The patient should be informed of the need to immediately inform the doctor about cases of unexpected muscle pain, muscle weakness or spasms, especially in combination with malaise and fever. CPK activity should be monitored in these patients. Therapy should be discontinued if CKD activity is 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 5 times lower than the upper limit of normal). If symptoms disappear and CPK activity returns to normal, consideration should be given to re-prescribing the drug or other HMG-CoA reductase inhibitors in smaller doses, with careful monitoring of the patient. Routine monitoring of CPK activity in the absence of symptoms of rhabdomyolysis is not advisable.

An increase in 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, azole antifungal drugs, 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 nicotinic acid should be carefully weighed.

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

In most cases, proteinuria decreases or disappears during therapy and does not indicate the occurrence of acute or progressive existing kidney disease.

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

Caution should be exercised when driving a car or working with increased concentration and psychomotor response (dizziness may occur during therapy).

Women of reproductive age should use adequate methods of contraception. Since cholesterol and substances synthesized from cholesterol are important for fetal development, the potential risk of HMG-CoA reductase inhibition exceeds the benefit of using the drug during pregnancy. In a study on rats (use in doses from 2-50 mg / kg / day) a decrease in fetal weight, a delay in bone ossification in the fetus, and a decrease in the survival rate of offspring were detected.

If pregnancy occurs during therapy, the drug should be discontinued immediately. There are no data on the excretion of rosuvastatin in women’s milk, so breast-feeding should be discontinued.

Active ingredient

Rosuvastatin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets