steroids side effects

Rosuvastatin dianabol results is a selective and competitive inhibitor of HMG-CoA reductase, an enzyme that converts Z-W-hydroxy-metilglyutarilkoenzim A to mevalonate which is a precursor of cholesterol. The primary target of action of rosuvastatin is the liver, where it is carried out the synthesis of cholesterol (LDL) and catabolism of low density lipoprotein (LDL) cholesterol.
Rosuvastatin increases the number of “liver” of LDL receptors on the cell surface, improving the capture and catabolism of LDL.
It also inhibits the synthesis of cholesterol, very low density lipoproteins (VLDL) in the liver cells, thereby reducing the total content of VLDL and LDL. Rosuvastatin decreases elevated cholesterol – LDL cholesterol (LDL-C), total cholesterol and triglycerides (TG), increases cholesterol in high density lipoprotein (HDL-C) and also reduces the content of apolipoprotein B (apoB), neLPVP cholesterol (total cholesterol minus HDL cholesterol, VLDL cholesterol, triglycerides, VLDL and increased levels of apolipoprotein AI (ApoA-1). Rosuvastatin reduces the ratio of LDL-C / HDL-C, total cholesterol / HDL-C,, neLPVP cholesterol / HDL-C and apoB / ApoA-1.
The therapeutic effect can be achieved within one week after initiation of treatment, 2 weeks reached 90% of the maximum possible effect. Generally, the highest possible therapeutic effect is achieved after 4 weeks and maintained by continued administration of the drug.

Clinical efficacy
Rosuvastatin is effective in the treatment of adult patients with hypercholesterolemia, hypertriglyceridemia with or without symptoms, regardless of their race, gender or age, as well as in the treatment of a particular category of patients with diabetes mellitus or hereditary form of familial hypercholesterolemia. Rosuvastatin is effective in treating patients with hypercholesterolemia type IIa and IIb according to Frederickson (mean baseline LDL-C about 4.8 mmol / l). In 80% of patients receiving 10 mg of rosuvastatin, the target values of LDL-C level, set by the European Society for the study of atherosclerosis (less than 3 mmol / l). Were achieved
in patients with heterozygous familial hypercholesterolemia treated with rosuvastatin at doses ranging from 20 mg to 80 mg for scheme for accelerated titration dose received all doses had a significant influence on the change of parameters characterizing lipid content, and the goal of therapy. As a result, dose titration to 40 mg per day (12 weeks) LDL-C content was reduced by 53%. In 33% of patients had achieved the values of LDL-C (less than 3 mmol / l) corresponding to the target standards of management of the European Society for the study of atherosclerosis.
In patients with homozygous familial hypercholesterolemia treated with rosuvastatin at doses of 20 and 40 mg, the mean reduction of LDL-C It amounted to 22%. An additive effect was observed in combination with fenofibrate in relation to TG content and nicotinic acid (more than 1 g per day) in respect of the content of HDL-C. Studies on the effect of rosuvastatin on the decrease in the number of complications caused by lipid disorders such as coronary heart disease, has not yet been completed.
In patients with low risk of coronary heart disease disease (defined as risk Framingham less than 10% for more than 10 years), with the average value of the content of LDL-cholesterol 4.0 mmol / l (154.5 mg / dl) rosuvastatin in a dose of 40 mg / day significantly slowed to increase the maximum value characterizing the carotid artery wall thickening in 12 segments, as compared to placebo at a rate -0.0145 mm / year (95% confidence interval (CI): from -0.0196 to – 0.0093, p <0.0001). The dose of 40 mg should be used only in patients with severe hypercholesterolaemia and high risk for cardiovascular disease.

Pharmacokinetics Absorption: Maximum rosuvastatin concentration in blood plasma is reached after 5 h after ingestion appropriate dose. The absolute bioavailability is approximately 20%. Distribution:Rosuvastatin is absorbed mainly by the liver, which is the main site of cholesterol synthesis and clearance of LDL-C metabolism. The volume of distribution of rosuvastatin is approximately 134 liters. 90% of rosuvastatin is bound to plasma proteins, mainly to albumin. Metabolism: undergoes limited metabolism (approximately 10%). Rosuvastatin is a fairly non-core substrate for the metabolic enzymes cytochrome P450 system. CYP2C9 is the major isoenzyme involved in metabolism, whereas isozymes CYP2C19, CYP3A4 and CYP2D6 in the metabolism are involved to a lesser extent. The major metabolite – N-desmethyl, which is 50% less active than rosuvastatin. Lactone metabolites are pharmacologically inactive. Over 90% of the pharmacological activity for the inhibition of the circulating HMG-CoA reductase inhibitor is provided with rosuvastatin, and the rest – its metabolites. Excretion: about 90% of the accepted dose of rosuvastatin is excreted unchanged from the body through the intestines (including adsorbed or absorbed rosuvastatin), and the remaining output unchanged to the kidneys. The half-life (Tm) is 19 hours, does not change with increasing dose. The geometric mean plasma clearance of approximately 50 l / h (coefficient of variation 21.7%). As in the case of other HMG-CoA reductase, a process of “hepatic” capture involved rosuvastatin membrane transporter of cholesterol through the membranes – C protein transport of organic anions. This vector plays an important role in the removal of rosuvastatin is the liver. Linearity: the systemic exposure of rosuvastatin increases in proportion to dose. Changes in the pharmacokinetic parameters when taking the drug several times a day is not marked. Age and sex: sex and age did not have a clinically meaningful effect on the pharmacokinetic parameters of rosuvastatin. Ethnic group: comparative pharmacokinetic study showed a twofold increase in the average value of AUC (area under the curve “concentration – time “) and TCmax (time to maximum plasma concentration of the drug) in patients of Asian origin (Japanese, Chinese, Filipino, Vietnamese and Koreans) compared with rates in Caucasians. Indians have been observed exceeding about 1.3 times the mean AUC and the C max – This analysis of the pharmacokinetic parameters for the entire study population revealed no clinically relevant differences in pharmacokinetics among Caucasian, Negroid races, Hispanics. Renal impairment: in patients with mild to moderate renal insufficiency plasma concentrations of rosuvastatin or N-desmethyl metabolite does not change significantly. In patients with severe renal failure (creatinine clearance (CC) of less than 30 ml / min.) Rosuvastatin plasma concentration of 3-fold higher concentration and N-desmethyl metabolite 9-fold higher compared with healthy volunteers. The concentration of rosuvastatin in the blood plasma of patients on hemodialysis was approximately 50% higher than in healthy volunteers. Hepatic impairment: in patients with varying degrees of hepatic failure with a score of 7 or less on the scale of Child-Pugh revealed no increase in T ½ rosuvastatin . However, 2 patients with a score of 8 and 9 on the Child-Pugh noted lengthening T ½ is approximately 2-fold higher than in patients with lower rates for the Child-Pugh. Experience in the use of rosuvastatin in patients with a score of higher than 9 on the scale of Child-Pugh is absent.

 

Indications

  • Hypercholesterolemia and combined (mixed) dyslipidemic state to reduce elevated levels of total cholesterol, LDL cholesterol, apolipoprotein B, and triglycerides in the serum as an adjunct to diet therapy when diet and other non-pharmacological methods (eg, exercise, weight loss) are insufficient.
  • Familial homozygous hypercholesterolemia as an adjunct to diet therapy and other methods of lipid-lowering therapy (eg, LDL-apheresis), or when such treatment is not effective enough.

Hypersensitivity to rosuvastatin or any of the components;

  • liver disease in its active phase, including a persistent increase in “liver” enzymes, as well as any increase in transaminase activity in serum of more than 3-fold compared dianabol results with the upper limit of normal;
  • pronounced renal dysfunction (creatinine clearance less than 30 ml / min.);
  • myopathy;
  • concomitant use of cyclosporine;
  • in patients predisposed to complications miotoksicheskih;
  • pregnancy and lactation;
  • women of childbearing age that do not use reliable contraception;
  • age of 18 years (effectiveness and safety have been established);
  • Patients with hepatic insufficiency with a score of higher than 9 on the scale of Childe-Pugh;
  • lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

40 mg tablet

  • Hypersensitivity to rosuvastatin or any of the components;
  • liver disease in its active phase, including a persistent increase in “liver” enzymes, as well as any increase in transaminase activity in serum of more than 3-fold compared with the upper limit of normal;
  • pronounced renal dysfunction (creatinine clearance less than 60 ml / min.);
  • myopathy;
  • concomitant use of cyclosporine;
  • in patients predisposed to complications miotoksicheskih;
  • pregnancy and lactation;
  • hypothyroidism;
  • personal or family history of muscle disease;
  • miotoksichnost in patients receiving other HMG-CoA reductase inhibitors or fibrates in history;
  • excessive alcohol consumption;
  • conditions that may lead to increased concentrations of rosuvastatin in blood plasma;
  • patients of Asian race;
  • concomitant use of fibrates;
  • age of 18 years (effectiveness and safety have been established);
  • Patients with hepatic insufficiency with a score of higher than 9 on the scale of Childe-Pugh;
  • lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

 

Precautions for tablets 5.10 mg and 20 mg of the risks of myopathy / rhabdomyolysis – kidney failure, hypothyroidism; personal or family history of hereditary muscular diseases and previous history of muscular toxicity with other HMG-CoA reductase inhibitor or fibrate; excessive alcohol consumption; a condition in which the observed increase in plasma concentrations of rosuvastatin; age over 70 years;history of liver disease; sepsis; hypotension; extensive surgery; trauma; severe metabolic, endocrine and electrolyte disorders; uncontrolled epilepsy; race (Asian); . concomitant use of fibrates for tablets of 40 mg of the risks of myopathy / rhabdomyolysis – renal failure; age over 70 years; history of liver disease; sepsis; hypotension; extensive surgery; trauma; severe metabolic, endocrine, or electrolyte disorders, uncontrolled epilepsy.

Application of pregnancy and lactation
Merten ® is contraindicated during pregnancy and lactation. Women of childbearing age should use reliable and adequate means of contraception.
Since cholesterol and cholesterol biosynthesis products are of great importance for the development of the fetus, the potential risk of inhibition of HMG-CoA reductase inhibitors outweigh the benefits of its use during pregnancy.
In the case of pregnancy, the drug should be discontinued immediately. Data on the allocation of the drug in breast milk are not available. If necessary, the appointment during lactation breastfeeding should be discontinued.

Dosage and administration
Before the treatment the patient should comply with the standard diet with low cholesterol foods, which should be continued during the treatment period. Doses should be individualized according to the purpose of treatment and therapeutic patient’s response to treatment, given the current generally accepted recommendations for target levels of lipids.
Inside, at any time, regardless of the meal, do not chew or crush, swallow whole, squeezed water.
The recommended starting dose is 5 mg or 10 mg 1 time per day for patients not previously treated with statins, and patients transferred to the reception of this drug after treatment with other inhibitors of HMG-CoA reductase. Choosing a starting dose should take into account the level of cholesterol in the individual patient, as well as the potential risk of development of cardiovascular complications and the potential risk of side effects. If necessary, after 4 weeks of dose adjustment can be performed. Due to the possibility of side effects while taking 40 mg dose compared to lower doses of the drug (see. Section “Side effects” ), a final titration to the maximum dose of 40 mg should be performed only in patients with severe hypercholesterolaemia and at high risk of heart -sosudistyh complications (particularly in patients with familial hypercholesterolemia) wherein when receiving a 20 mg dose was not reached the target cholesterol levels, and which will be under medical supervision. In appointing the 40 mg dose recommended careful medical supervision. Not recommended the appointment of a 40 mg dose in patients not previously accessed a doctor Elderly patients For patients older than 70 years, the recommended starting dose is 5 mg. Dose adjustment based on age is not required. Patients with renal insufficiency In patients with renal insufficiency, mild or moderate dose adjustment is required. The recommended starting dose is 5 mg in patients with moderate renal impairment (creatinine clearance less dianabol results than 60 mL / min.). Appointment of Merten ® at any dose is contraindicated in patients with severe renal insufficiency (see. “Contraindications”). Patients with renal insufficiency, moderate use of the drug at a dose of 40 mg is contraindicated. Patients with hepatic impairment increased systemic concentrations of rosuvastatin in patients with a score on the scale of Child-Pugh equal to 7 and below, have been identified. However, the increase in systemic concentrations of the drug were observed in patients with scores on the scale of Child-Pugh 8 and 9. In these patients, liver function should be monitored during therapy. These patients received a drug with a score on the scale of Child-Pugh above 9 no. Patients with liver disease in the active phase of Merten ® is contraindicated. Ethnic groups in patients of Asian race, may increase the systemic concentration of rosuvastatin. At doses of 10 mg and 20 mg the recommended starting dose for Asian patients is 5 mg. Use of the drug at a dose of 40 mg in these patients is contraindicated (see. Section “Contraindications” ). Patients predisposed to myopathy at doses 10 and 20 mg of the recommended initial dose for patients with a predisposition to myopathy is 5 mg. Use of the drug at a dose of 40 mg is contraindicated in such patients.