Rosuvastatin pills 20mg №90

Adverse Effects

The side effects observed when taking the drug Rosuvastatin, usually expressed slightly and pass on their own. As with the use of other inhibitors of HMG-CoA reductase, the frequency of side effects is mainly dose-dependent.

The incidence of adverse effects is presented in accordance with the classification of the World Health Organization: often (> 1/100, <1/10); infrequently (> 1/1000, <1/100); rarely (> 1/10000, <1/1000); very rarely (<1/10000), unspecified frequency (cannot be calculated from the available data).

The immune system: rarely, hypersensitivity reactions, including angioedema.

Endocrine system: often - type 2 diabetes.

From the side of the central nervous system: often - headache, dizziness.

From the digestive tract: often - constipation, nausea, abdominal pain; rarely - pancreatitis.

From the skin: infrequently - pruritus, rash, urticaria.

From the musculoskeletal system: often myalgia; rarely - myopathy (including myositis), rhabdomyolysis.

Other: often - asthenic syndrome.

From the urinary system

Patients treated with rosuvastatin may have proteinuria. Changes in the amount of protein in the urine (from the absence or trace amounts to ++ or more) are observed in less than 1% of patients receiving 10-20 mg of the drug, and in approximately 3% of patients receiving 40 mg of the drug. A slight change in the amount of protein in the urine was noted when taking a dose of 20 mg. In most cases, proteinuria diminishes or disappears during therapy and does not mean the onset or the progression of an existing kidney disease.

From the musculoskeletal system

When using the drug Rosuvastatin in all doses, and especially when taking doses of the drug in excess of 20 mg, the following effects on the musculoskeletal system were reported: myalgia, myopathy (including myositis), in rare cases - rhabdomyolysis with or without acute renal failure.

A dose-dependent increase in the activity of creatine phosphokinase (CPK) is observed in an insignificant number of patients taking rosuvastatin.In most cases, it was minor, asymptomatic and temporary. In the case of increased activity of CPK (more than 5 times compared with the upper limit of the norm), therapy should be suspended (see the section "Special Instructions").

Liver

With the use of rosuvastatin, a dose-dependent increase in the activity of liver transaminases is observed in a small number of patients. In most cases, it is insignificant, asymptomatic and temporary.

Laboratory values

When using the drug Rosuvastatin, the following changes in laboratory parameters were also observed: an increase in the concentration of glucose, bilirubin, the activity of gamma-glutamyl transpeptidase, alkaline phosphatase, thyroid dysfunction.

Post-marketing application

The following side effects have been reported in the post-marketing use of Rosuvastatin:

From the hemopoietic system: unspecified frequency - thrombocytopenia.

From the digestive tract: very rarely - jaundice, hepatitis; rarely, increased activity of liver transaminases; unspecified frequency - diarrhea.

From the musculoskeletal system: very rarely - arthralgia; unspecified frequency - immune-mediated necrotizing myopathy.

From the side of the central nervous system: very rarely - loss or loss of memory; unspecified frequency - peripheral neuropathy.

On the part of the respiratory system: unspecified frequency - cough, shortness of breath.

From the urinary system: very rarely - hematuria.

From the skin and subcutaneous fat: unspecified frequency - Stevens-Johnson syndrome.

On the part of the reproductive system and the breast: unspecified frequency - gynecomastia.

Other: unspecified frequency - peripheral edema.

When using certain statins, the following side effects were reported: depression, sleep disturbance, including insomnia and nightmares, sexual dysfunction, hyperglycemia, and an increase in the concentration of glycated hemoglobin. It was reported on isolated cases of interstitial lung disease, especially with prolonged use of drugs (see section "Special instructions").

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

- · hypersensitivity to rosuvastatin or any of the components of the drug;

- · lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the product contains lactose);

- · children's age up to 18 years;

- · liver disease in the active phase, including a persistent increase in serum transaminase activity and any increase in serum transaminase activity (more than 3 times compared with the upper limit of normal);

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

- · myopathy and predisposition to the development of myotoxic complications;

- · simultaneous administration of cyclosporine;

- · in women: pregnancy, breastfeeding period, 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;

- · lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the product contains lactose);

- · children's age up to 18 years;

- · simultaneous administration of cyclosporine;

- · in women: pregnancy, breastfeeding period, lack of adequate methods of contraception;

- · liver disease in the active phase, including a persistent increase in serum transaminase activity and any increase in serum transaminase activity (more than 3 times compared with the upper limit of normal) in patients with risk factors for myopathy / rhabdomyolysis, namely:

- · renal failure of moderate severity (CC less than 60 ml / min);

- · hypothyroidism;

- · personal or family history of muscular diseases;

- · myotoxicity while taking other HMG-CoA reductase inhibitors or a history of fibrates;

- · excessive drinking;

- · conditions that can lead to increased plasma concentrations of rosuvastatin;

- · simultaneous intake of fibrates;

- · use in patients of the Mongoloid race.

Carefully

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

The risk of myopathy / rhabdomyolysis is renal failure, hypothyroidism, personal or family history of hereditary muscular diseases, and a previous history of muscle toxicity when using other HMG-CoA reductase inhibitors (statins) or fibrates; excessive drinking; age over 65; states thatat which increase in plasma concentration of rozuvastatin is noted; race (mongoloid race); simultaneous administration with fibrates (see Pharmacokinetics section); history of liver disease; sepsis; hypotension; extensive surgical interventions, injuries, severe metabolic, endocrine or electrolyte disorders or uncontrolled seizures.

For the drug in a daily dose of 40 mg

Renal failure mild severity (CC more than 60 ml / min); age over 65; history of liver disease; sepsis; hypotension; extensive surgical interventions, injuries, severe metabolic, endocrine or electrolyte disorders or uncontrolled seizures.

Patients with liver failure

There is no data or experience of using the drug in patients with more than 9 points on the Child-Pugh scale (see the sections Pharmacodynamics and Special Instructions).

Rosuvastatin is contraindicated during pregnancy and during breastfeeding.

Women of reproductive age should use adequate methods of contraception.

Since cholesterol and other cholesterol biosynthesis products are important for fetal development, the potential risk of inhibition of HMG-CoA reductase exceeds the benefits of using the drug in pregnant women.

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

Data regarding the allocation of rosuvastatin with breast milk are not available, so during breastfeeding, the drug should be stopped (see "Contraindications").

The use of the drug in a daily dose of 5 mg, 10 mg, 20 mg and 40 mg in patients with liver disease in the active phase, including a persistent increase in serum transaminase activity and any increase in serum transaminase activity (more than 3 times compared with the upper limit of normal ) is contraindicated.

To use the drug with caution in a daily dose of 5 mg, 10 mg, 20 mg and 40 mg in patients with a history of liver disease.

The use of the drug in a daily dose of 5 mg, 10 mg and 20 mg in patients with severe impaired renal function (CC less than 30 ml / min) is contraindicated.

The use of the drug in a daily dose of 40 mg is contraindicated in patients with moderately severe renal failure (CC less than 60 ml / min)

To use the drug with caution in a daily dose of 5 mg, 10 mg and 20 mg in patients with renal insufficiency.

With caution, use the drug in a daily dose of 40 mg in patients with low-grade renal insufficiency (CC more than 60 ml / min).

Patients with moderate renal impairment are recommended an initial dose of 5 mg.

The use of the drug in children and adolescents under the age of 18 years is contraindicated.

Dose adjustment is not required to elderly patients.

Renal effects

Patients who received high doses of Rosuvastatin (mainly 40 mg) received tubular proteinuria, which in most cases was transient. Such proteinuria did not indicate acute kidney disease or progression of kidney disease. In patients taking the drug in a dose of 40 mg, it is recommended to monitor indicators of renal function during treatment.

From the musculoskeletal system

When using the drug Rosuvastatin in all doses, and especially when taking doses of the drug in excess of 20 mg, the following effects on the musculoskeletal system were reported: myalgia, myopathy, in rare cases rhabdomyolysis.

Determination of creatine phosphokinase activity

Determination of CPK activity should not be carried out after intense physical exertion or in the presence of other possible reasons for an increase in CPK activity, which may lead to a misinterpretation of the results obtained. If the initial activity of CPK is significantly increased (5 times higher than the upper limit of the norm), after 5-7 days it is necessary to re-measure. Do not start therapy if the repeated test confirms the initial activity of CPK (more than 5 times higher than the upper limit of normal).

Before the start of therapy

When prescribing Rosuvastatin, as well as prescribing other HMG-CoA reductase inhibitors, caution should be exercised in patients with existing risk factors for myopathy / rhabdomyolysis., (cm.section "C caution") it is necessary to consider the ratio of risk and possible benefits of therapy and conduct clinical observation.

During therapy

The patient should be informed of the need to immediately report to the doctor about cases of sudden onset of muscle pain, muscle weakness or spasms, especially in combination with indisposition and fever. In such patients, the activity of CK should be determined.. Therapy should be discontinued if the activity of CPK is significantly increased (more than 5 times compared with the upper limit of the norm) or if the symptoms of the muscles are pronounced and cause daily discomfort (even if the activity of CPK is increased no more than 5 times compared to with the upper limit of the norm). If the symptoms disappear, and the activity of CPK returns to normal, consideration should be given to reappointment of the drug Rosuvastatin or other HMG-CoA reductase inhibitors in smaller doses with careful monitoring of the patient. Routine control of CPK activity in the absence of symptoms is not appropriate.

Very rare cases of immune-mediated necrotizing myopathy with clinical manifestations in the form of persistent weakness of the proximal muscles and an increase in the activity of CPK in the blood serum during treatment or when discontinuation of statins, including, have been observed. Rosuvastatin. Additional studies of the muscular and nervous systems, serological studies, and therapy with immunosuppressive agents may be required.

There are no signs of increased effects on skeletal muscles when taking the drug Rosuvastatin and concomitant therapy. However, an increase in the incidence of myositis and myopathy was reported in patients taking other HMG-CoA reductase inhibitors in combination with fibrin acid derivatives, including gemfibrozil, cyclosporine, nicotinic acid in lipid-lowering doses (more than 1 g / day), azole antifungal agents, inhibitors HIV proteases and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when used together with some HMG-CoA reductase inhibitors. Thus, the simultaneous use of the drug Rosuvastatin and gemfibrozil is not recommended. The balance of risk and potential benefit should be carefully weighed in when using the drug Rosuvastatin together with fibrates or lipid-lowering doses of nicotinic acid. Rosuvastatin 40 mg in conjunction with fibrates is contraindicated (see sections "Interaction with other drugs and other forms of drug interaction", "Contraindications").

After 2-4 weeks after the start of treatment and / or with an increase in the dose of the drug Rosuvastatin, monitoring of lipid metabolism indices is necessary (dose adjustment is necessary if necessary).

Liver

It is recommended to determine the indicators of liver function before the start of therapy and 3 months after the start of therapy.Taking the drug Rosuvastatin should be stopped or the dose should be reduced if the activity of liver transaminases in serum is 3 times higher than the upper limit of normal.

In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, the treatment of major diseases should be carried out 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 observed compared with indicators obtained among European patients (see the sections “Dosage and administration” and “Pharmacokinetics”).

HIV protease inhibitors

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

Lactose

The drug should not be used in patients with lactase deficiency, lactose intolerance and glucose-galactose malabsorption.

Interstitial lung disease

With the use of some statins, especially for a long time, isolated cases of interstitial lung disease have been reported. Manifestations of the disease can be shortness of breath, unproductive cough and worsening of general well-being (weakness, weight loss and fever). If interstitial lung disease is suspected, statin therapy should be discontinued.

Type 2 diabetes

In patients with a glucose concentration of 5.6 to 6.9 mmol / l, therapy with Rosuvastatin was associated with an increased risk of developing type 2 diabetes.

Influence on ability to drive a car and other mechanisms

No studies have been conducted to study the effect of Rosuvastatin on the ability to drive and use mechanisms. Care should be taken when driving or working that requires increased concentration and psychomotor speed (dizziness, weakness may occur during therapy).

When several daily doses are taken simultaneously, the pharmacokinetic parameters of rosuvastatin do not change.

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

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

Drug interaction

Effect of the use of other drugs on rosuvastatin

Transport protein inhibitors: Rosuvastatin binds to certain transport proteins, in particular, OATP1B1 and BCRP.The concomitant use of drugs that are inhibitors of these transport proteins may be accompanied by an increase in plasma concentration of rosuvastatin and an increased risk of myopathy (see Table 1 and the sections "Dosage and administration" and "Special instructions").

Cyclosporine: with simultaneous use of rosuvastatin and cyclosporine, the AUC of rosuvastatin was on average 7 times higher than the value observed in healthy volunteers (see table 1). It does not affect the plasma concentration of cyclosporine. Rosuvastatin is contraindicated in patients taking cyclosporine (see section "Contraindications").

Human immunodeficiency Virus (HIV) Protease Inhibitors: Although the exact mechanism of interaction is unknown, co-administration of HIV protease inhibitors can lead to a significant increase in exposure to rosuvastatin (see Table 1). A pharmacokinetic study on the simultaneous use of 20 mg of rosuvastatin with a combination preparation containing two HIV protease inhibitors (400 mg of lopinavir / 100 mg of ritonavir) in healthy volunteers resulted in an approximately twofold and fivefold increase in AUC_(0-24) andC_max Rosuvastatin, respectively. Therefore, the concomitant use of rosuvastatin and HIV protease inhibitors is not recommended (see sections "Dosage and administration", "Special instructions", table 1).

Gemfibrozil and other lipid-lowering drugs: the combined use of rosuvastatin and gemfibrozil results in a 2-fold increase in the maximum concentration of rosuvastatin in the blood plasma and AUC of rosuvastatin (see the section "Special Instructions").Based on data on specific interactions, pharmacokinetically significant interactions with fenofibrate are not expected; pharmacodynamic interactions are possible.

Gemfibrozil, fenofibrate, other fibrates and lipid-lowering doses of nicotinic acid (more than 1 g / day) increased the risk of myopathy while being used with HMG-CoA reductase inhibitors, possibly due to the fact that they can cause myopathy when used in monotherapy (see section "Special instructions"). While taking the drug with gemfibrozil, fibrates, nicotinic acid in lipid-lowering doses (more than 1 g / day), an initial dose of 5 mg is recommended for patients, 40 mg is contraindicated when taken together with fibrates (see "Contraindications", "Method use and dose "," Special instructions ").

Ezetimibe: simultaneous use of the drug Rosuvastatin at a dose of 10 mg and ezetimibe at a dose of 10 mg was accompanied by an increase in the AUC of rosuvastatin in patients with hypercholesterolemia (see table 1). An increase in the risk of side effects due to the pharmacodynamic interaction between Rosuvastatin and ezetimib cannot be ruled out.

Antacids: the simultaneous use of rosuvastatin and suspensions of antacids containing Magnesium and aluminum hydroxide, reduces the plasma concentration of rosuvastatin by about 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: the simultaneous use of rosuvastatin and Erythromycin leads to a decrease in the AUC of rosuvastatin by 20% and C_max Rosuvastatin by 30%. Such an interaction may occur as a result of increased intestinal motility caused by taking erythromycin.

Isoenzymes of cytochrome P450: In vivo and in vitro results showed that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. In addition, rosuvastatin is a weak substrate for these isoenzymes. Therefore, the interaction of rosuvastatin with other drugs at the metabolic level with the participation of cytochrome P450 is not expected. The clinically significant interaction of rosuvastatin with Fluconazole (an inhibitor of isoenzymes CYP2C9 and CYP3A4) and Ketoconazole (an inhibitor of isoenzymes CYP2A6 and CYP3A4) was not observed.

Fuzidovaya acid: research on the interaction of rosuvastatin and fusidic acid has not been conducted; as with the use of other statins, post-marketing reports were received of cases of rhabdomyolysis with simultaneous use of rosuvastatin and fusidic acid; It is necessary to monitor patients and, if necessary, it is possible to temporarily stop taking rosuvastatin.

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

The dose of the drug Rosuvastatin should be adjusted, if necessary, its combined use with drugs that increase the exposure to rosuvastatin.You should read the instructions for use of these drugs before their appointment simultaneously with the drug Rosuvastatin. If exposure is expected to increase by 2 times or more, the initial dose of the drug Rosuvastatin should be 5 mg 1 time / day. The maximum daily dose of Rosuvastatin should also be adjusted so that the expected exposure to rosuvastatin does not exceed that for a dose of 40 mg taken without the simultaneous administration of drugs interacting with rosuvastatin. For example, the maximum daily dose of the drug Rosuvastatin while applying