Rosuvastatin-Vertex, 20 mg 90 pcs

Directions for use

Orally, do not chew or crush the tablet, swallow it whole with water. The drug may be administered at any time of the day regardless of the time of food intake. Before the start of therapy with Rosuvastatin the patient should start a standard hypocholesterolemic diet and continue 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 concentrations.

The recommended starting dose for patients starting to take the drug or for patients transferred from other HMG-CoA reductase inhibitors should be 5 or 10 mg of Rosuvastatin once daily. When choosing the initial dose, individual cholesterol content should be guided and possible risk of cardiovascular complications should be taken into account, as well as the potential risk of side effects should be assessed. If necessary, the dose may be increased to a larger one in 4 weeks.

In connection with the possible development of side effects when taking the dose of 40 mg, compared with lower doses of the drug (see. Due to the possible development of side effects of 40 mg dose compared to lower doses of the drug (see section “Side effects”), 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 result was not achieved while taking the 20 mg dose and will be under the supervision of a specialist.

Especially close monitoring of patients receiving the 40 mg dose is recommended. It is not recommended to prescribe the 40 mg dose to patients who have not previously seen a physician. After 2-4 weeks of therapy and/or when increasing the dose of the drug Rosuvastatin it is necessary to monitor the parameters of lipid metabolism (if necessary, a dose adjustment is required).

The use of the drug in a higher dose than 40 mg is not justified in connection with the increase in the side effects and in most cases is not recommended.

Elderly patients
No dose adjustment is required.

Patients with renal insufficiency
In patients with mild to moderate renal insufficiency, no dose adjustment is required. In patients with severe renal failure (CKD less than 30 ml/min) the use of Rosuvastatin is contraindicated.

The drug administration in a dose of 40 mg is contraindicated in patients with moderate renal impairment (CK 30-60 ml/min)
Patients with moderate renal impairment should receive a starting dose of the drug 5 mg.

Patients with hepatic insufficiency
Rosuvastatin is contraindicated in patients with liver disease in the active phase Special populations. Ethnic groups When 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 “Cautions”). This fact should be considered when prescribing Rosuvastatin to these groups of patients.

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

Genetic polymorphisms
Carriers of SLCO1B1 (OATP1B1) genotype c.521CC and ABCG2 (BCRP) genotype c.421AA had increased exposure (AUC) to rosuvastatin compared with SLCO1B1 c.521TT and ABCG2 c.421CC genotype carriers. For patients-carriers of c.521CC or c.421AA genotypes, the recommended maximum dose of the drug Rosuvastatin is 20 mg once daily.

Patients with predisposition to myopathy
Administration of the drug in dose of 40 mg is contraindicated in patients with factors that may indicate predisposition to myopathy. When prescribing doses of 10 and 20 mg the recommended initial dose for this group of patients is 5 mg

Companion therapy
Rosuvastatin binds to various transport proteins (in particular to OATP1B1 and BCRP). When co-administration of the drug Rosuvastatin with drugs (such as cyclosporine, some HIV protease inhibitors, including the combination of ritonavir 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.

In such cases, the possibility of prescribing alternative therapy or temporary discontinuation of Rosuvastatin should be assessed. If the use of the above drugs is necessary, the benefit-risk ratio of concomitant therapy with Rosuvastatin should be assessed and the possibility of reducing its dose should be considered.

Special Instructions

In patients receiving high doses of rosuvastatin (particularly 40 mg/day), tubular proteinuria has been observed, which was detected with test strips and in most cases was intermittent or transient.

Such proteinuria is not indicative of acute disease or progression of concomitant renal disease. The incidence of serious renal function abnormalities noted in a post-marketing study of rosuvastatin is higher at the 40 mg/day dose.

In patients taking the drug at a dose of 30 or 40 mg/day, it is recommended to monitor renal function parameters during treatment (at least once every 3 months). Effect on the musculoskeletal system.

When using rosuvastatin at all doses, but especially at doses exceeding 20 mg/day, the following effects on the musculoskeletal system have been reported: myalgia, myopathy, in rare cases rhabdomyolysis.

Very rare cases of rhabdomyolysis have been reported with concomitant use of HMG-CoA reductase inhibitors and ezetimibe. Such combination should be used with caution because pharmacodynamic interaction cannot be excluded. As in the case of other HMG-CoA reductase inhibitors, the incidence of rhabdomyolysis during post-marketing use of rosuvastatin is higher when using 40 mg/day dose. Determination of CPK activity.

CPK activity should not be determined after vigorous physical activity and in the presence of other possible causes of increase in its activity; it may lead to misinterpretation of the obtained results. If the baseline CPK activity is significantly exceeded (5 times the ULN), the analysis should be repeated in 5-7 days.

The therapy should not be started if the results of the repeated test confirm the initial high activity of CPK (more than 5 times the ULN). Before therapy Depending on the daily dose in patients with existing risk factors for myopathy/rhabdomyolysis, rosuvastatin is either contraindicated or should be administered with caution (see “Contraindications”, “Limitations of Use”).

Such factors include: renal dysfunction; hypothyroidism; muscle diseases in the anamnesis (includingincluding familial); myotoxic phenomena when taking other HMG-CoA reductase inhibitors or fibrates in the history; excessive use of alcohol; age over 65 years; conditions in which plasma concentrations of rosuvastatin may increase; concomitant use of fibrates.

In such patients it is necessary to assess the risk and possible benefit of therapy. Clinical monitoring is also recommended. If baseline CPK activity is more than 5-fold higher than ICH, rosuvastatin therapy should not be started.

During therapy with rosuvastatin the patient should be informed to seek immediate medical attention in case of sudden onset of muscle pain, muscle weakness or cramps, especially in combination with malaise and fever. In such patients, CPK activity should be determined. The therapy should be stopped if CPK activity is significantly increased (more than 5 times of IGN) or muscle symptoms are severe and cause daily discomfort (even if CPK activity is not more than 5 times of IGN).

If symptoms disappear and CPK activity returns to normal, resumption of rosuvastatin or other HMG-CoA reductase inhibitors at lower doses with close medical supervision should be considered. Monitoring of CPK activity in the absence of symptoms is unnecessary.

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 therapy or upon discontinuation of HMG-CoA reductase inhibitors, including rosuvastatin.

Additional muscular and nervous system studies, serological studies and therapy with immunosuppressive agents may be required. No evidence of increased skeletal muscle effects with rosuvastatin and concomitant therapy has been noted.

However an increase in myositis and myopathy has been reported in patients taking other HMG-CoA reductase inhibitors in combination with fibric acid derivatives (e.g. gemfibrozil), cyclosporine, nicotinic acid at lipid-lowering doses (over 1 g/day), antifungal agents – azole derivatives, HIV protease inhibitors and macrolide antibiotics.

Simultaneous use with some HMG-CoA reductase inhibitors increases the risk of myopathy. Thus, concomitant use of rosuvastatin and gemfibrozil is not recommended. The benefits of further changes in plasma lipid concentrations when combining this drug with fibrates or nicotinic acid in lipid-lowering doses should be carefully weighed against the possible risk.

Rosuvastatin at a dose of 30 mg/day is contraindicated for combination therapy with fibrates. Due to the increased risk of rhabdomyolysis, rosuvastatin should not be used in patients with acute conditions that may lead to myopathy or conditions predisposing to the development of renal failure (such as sepsis, arterial hypotension, extensive surgery, trauma, severe metabolic, endocrine and electrolyte disorders or uncontrolled seizures).

Liver. Depending on the daily dose, rosuvastatin is contraindicated or should be used with caution in patients with excessive alcohol consumption and/or with a history of liver disease (see “Contraindications”, “Limitations on use”).

It is recommended to determine liver function tests before the therapy start and 3 months after the start of therapy. Rosuvastatin should be discontinued or the dose of this agent should be reduced if hepatic serum transaminase activity exceeds 3 times VHF.

In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome before treatment with rosuvastatin therapy of underlying diseases should be conducted. Ethnic peculiarities. During pharmacokinetic studies, increased plasma concentrations of rosuvastatin have been observed in mongoloid race compared to Caucasoid race. Interstitial lung disease.

Single cases of interstitial lung disease have been reported with some HMG-CoA reductase inhibitors, especially for long periods of time. Manifestations of the disease may include shortness of breath, non-productive cough and deterioration of general well-being (weakness, weight loss and fever).

If interstitial lung disease is suspected, therapy with HMG-CoA reductase inhibitors should be discontinued. Diabetes mellitus type 2. In patients with glucose concentrations between 5.6 and 6.9 mmol/L, therapy with rosuvastatin has been associated with an increased risk of developing type 2 diabetes mellitus. Influence on the ability to drive a car or perform work requiring increased speed of physical and mental reactions.

Studies to study the effect of rosuvastatin on the ability to drive vehicles and work with mechanisms have not been conducted. Nevertheless, taking into account the possibility of dizziness and other side effects, caution should be exercised when driving vehicles and operating other mechanisms that require high concentration and rapid psychomotor reactions.

Contraindications

Daily dose up to 30 mg: hypersensitivity to rosuvastatin; liver disease in the active phase (including a persistent increase in hepatic transaminase activity and an increase in serum hepatic transaminase activity more than 3-fold compared to CHF); severe renal failure (creatinine cl)

Daily dose of 30 mg or more: hypersensitivity to rosuvastatin; liver disease in the active phase (including persistent increase in hepatic transaminase activity and increase in serum hepatic transaminase activity more than 3 times compared to IGN); moderate to severe renal failure (creatinine Cl)