Rosuvastatin: indications, contraindications, instructions for use

Indications and contraindications for the use of Rosuvastatin

There are two main indications for taking this drug:

1. Hypercholesterolemia.
2. Hypertriglyceridemia.

It should be noted that, together with treatment with Rosuvastatin, strict adherence to the diet prescribed by the doctor is mandatory. Otherwise, the effectiveness of the drug is sharply reduced.

The use of the drug is limited if patients have the following conditions:

• The presence of individual hypersensitivity to the main or additional ingredients of the drug.
• Acute and chronic liver diseases.
• Myopathy.
• Chronic kidney disease.
• Pregnancy and breastfeeding period.
• Sepsis.
• Severe injuries.

If there are serious indications, Rosuvastatin can be prescribed with extreme caution to patients with endocrine pathology, as well as to patients under the age of 18 and over 60 years of age.

Adverse reactions and symptoms of overdose

Taking the drug may be accompanied by a large number of side effects. Most often, patients develop the following conditions:

• From the musculoskeletal system: arthritis, myositis, myopathies.
• CNS: headaches, dizziness, sleep disturbances, anxiety, depressive thoughts.
• From the respiratory system: cough, bronchial asthma, rhinitis, pharyngitis, tracheitis, bronchitis and pneumonia.
• Urinary tract infections.
• Gastrointestinal tract: dyspeptic syndrome, bloating, gastritis.
• From the cardiovascular system: tachycardia or angina.
• Allergic reactions.

An overdose of the drug is currently not described.

Rosuvastatin 30 film-coated tablets 10 mg

Registration Certificate Holder

IZVARINO PHARMA (Russia)

Dosage form

Medicine - Rosuvastatin

Description

Film-coated tablets

white or almost white, round, biconvex; on a cross section, the core is white or almost white.

1 tab.

rosuvastatin calcium 10.4 mg, which corresponds to the content of rosuvastatin 10 mg

Excipients

: anhydrous lactose - 93.525 mg, calcium carbonate - 22.5 mg, crospovidone - 4.05 mg, potato starch - 2.5 mg, magnesium stearate - 1.35 mg, colloidal silicon dioxide - 0.675 mg.

Shell composition:

Opdry II white (85F18422) - 5 mg (polyvinyl alcohol - 2 mg, titanium dioxide - 1.25 mg, macrogol 3350 - 1.01 mg, talc - 0.74 mg).

10 pieces. — contour cellular packaging (1) — cardboard packs. 10 pieces. — contour cellular packaging (2) — cardboard packs. 10 pieces. — contour cellular packaging (3) — cardboard packs. 10 pieces. — contour cellular packaging (4) — cardboard packs. 10 pieces. — contour cellular packaging (5) — cardboard packs. 10 pieces. — contour cellular packaging (6) — cardboard packs. 10 pieces. — contour cellular packaging (8) — cardboard packs. 10 pieces. — contour cellular packaging (9) — cardboard packs. 14 pcs. — contour cellular packaging (1) — cardboard packs. 14 pcs. — contour cellular packaging (2) — cardboard packs. 14 pcs. — contour cellular packaging (3) — cardboard packs. 14 pcs. — contour cellular packaging (4) — cardboard packs. 14 pcs. — contour cellular packaging (5) — cardboard packs. 14 pcs. — contour cellular packaging (6) — cardboard packs. 14 pcs. — contour cellular packaging (8) — cardboard packs. 14 pcs. — contour cellular packaging (9) — cardboard packs. 15 pcs. — contour cellular packaging (1) — cardboard packs. 15 pcs. — contour cellular packaging (2) — cardboard packs. 15 pcs. — contour cellular packaging (3) — cardboard packs. 15 pcs. — contour cellular packaging (4) — cardboard packs. 15 pcs. — contour cellular packaging (5) — cardboard packs. 15 pcs. — contour cellular packaging (6) — cardboard packs. 15 pcs. — contour cellular packaging (8) — cardboard packs. 15 pcs. — contour cellular packaging (9) — cardboard packs.

Indications

Hypercholesterolemia (type IIa, including familial heterozygous hypercholesterolemia) or mixed hypercholesterolemia (type IIb) as an adjunct to diet when diet and other non-drug treatments (eg, exercise, weight loss) are insufficient.

Familial homozygous hypercholesterolemia as an adjunct to diet and other cholesterol-lowering therapy or in cases where such therapy is not suitable for the patient.

Contraindications for use

Liver diseases in the active phase (including a persistent increase in the activity of hepatic transaminases or any increase in the activity of transaminases more than 3 times compared with ULN), severe renal dysfunction (creatinine clearance <30 ml/min), myopathy, concomitant use of cyclosporine, pregnancy, lactation (breastfeeding), women of reproductive age who do not use adequate methods of contraception, children and adolescents under 18 years of age, increased sensitivity to rosuvastatin.

pharmachologic effect

A lipid-lowering drug from the statin group, an inhibitor of HMG-CoA reductase. According to the principle of competitive antagonism, the statin molecule binds to the part of the coenzyme A receptor where this enzyme is attached. Another part of the statin molecule inhibits the conversion of hydroxymethyl glutarate to mevalonate, an intermediate in the synthesis of the cholesterol molecule. Inhibition of the activity of HMG-CoA reductase leads to a series of sequential reactions, as a result of which the intracellular cholesterol content decreases and a compensatory increase in the activity of LDL receptors occurs and, accordingly, accelerates the catabolism of LDL cholesterol (Xc).

The lipid-lowering effect of statins is associated with a decrease in the level of total cholesterol due to LDL cholesterol. The decrease in LDL levels is dose-dependent and is not linear, but exponential.

Statins do not affect the activity of lipoprotein and hepatic lipases, do not have a significant effect on the synthesis and catabolism of free fatty acids, therefore their effect on TG levels is secondary and indirect through their main effects on reducing LDL-C levels. The moderate decrease in TG levels during statin treatment appears to be associated with the expression of remnant (apo E) receptors on the surface of hepatocytes involved in the catabolism of DILI, which contain approximately 30% TG.

In addition to the lipid-lowering effect, statins have a positive effect on endothelial dysfunction (a preclinical sign of early atherosclerosis), on the vascular wall, the condition of atheroma, improve the rheological properties of blood, and have antioxidant and antiproliferative properties.

The therapeutic effect appears within 1 week. after the start of therapy and after 2 weeks of treatment is 90% of the maximum possible effect, which is usually achieved by week 4 and remains constant thereafter.

Drug interactions

With the simultaneous use of rosuvastatin and cyclosporine, the AUC of rosuvastatin was on average 7 times higher than the value observed in healthy volunteers, while the plasma concentration of cyclosporine did not change.

Initiating rosuvastatin therapy or increasing the dose of the drug in patients receiving concomitant vitamin K antagonists (eg, warfarin) may lead to an increase in prothrombin time and INR, and discontinuation of rosuvastatin or dose reduction may lead to a decrease in the INR (INR monitoring is recommended in such cases).

The combined use of rosuvastatin and gemfibrozil leads to a 2-fold increase in Cmax in blood plasma and AUC of rosuvastatin.

The simultaneous use of rosuvastatin and antacids containing aluminum and magnesium hydroxide leads to a decrease in the plasma concentration of rosuvastatin by approximately 50%. This effect is less pronounced if antacids are used 2 hours after taking rosuvastatin (clinical significance unknown).

The simultaneous use of rosuvastatin and erythromycin leads to a decrease in rosuvastatin AUC by 20% and rosuvastatin Cmax by 30% (probably as a result of increased intestinal motility caused by erythromycin).

Concomitant use of rosuvastatin and oral contraceptives increases the AUC of ethinyl estradiol and AUC of norgestrel by 26% and 34%, respectively. Such an interaction cannot be excluded with the simultaneous use of rosuvastatin and hormone replacement therapy.

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

Co-administration of rosuvastatin and itraconazole (CYP3A4 inhibitor) increases the AUC of rosuvastatin by 28% (clinically insignificant).

Dosage regimen

Taken orally. The recommended starting dose is 10 mg 1 time/day. If necessary, the dose can be increased to 20 mg after 4 weeks. Increasing the dose to 40 mg is possible only in patients with severe hypercholesterolemia and a high risk of cardiovascular complications (especially in patients with familial hypercholesterolemia) with insufficient effectiveness at a dose of 20 mg and subject to physician supervision.

Side effect

From the side of the central nervous system:

often - headache, dizziness, asthenic syndrome; possibly anxiety, depression, insomnia, neuralgia, paresthesia.

From the digestive system:

: often - constipation, nausea, abdominal pain; possible - reversible transient dose-dependent increase in the activity of liver transaminases, dyspepsia (including diarrhea, flatulence, vomiting), gastritis, gastroenteritis.

From the respiratory system

: often – pharyngitis; possible – rhinitis, sinusitis, bronchial asthma, bronchitis, cough, dyspnea, pneumonia.

From the cardiovascular system:

possible – angina pectoris, increased blood pressure, palpitations, vasodilation.

From the musculoskeletal system:

often – myalgia; possible – arthralgia, arthritis, muscle hypertonicity, back pain, pathological pearl 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); possible - peripheral edema (arms, legs, ankles, legs), pain in the lower abdomen, urinary tract infections.

Allergic reactions:

possible - skin rash, itching;
rarely – angioedema. From the laboratory parameters:
transient dose-dependent increase in CPK activity (if CPK activity increases by more than 5 times compared to ULN, therapy should be temporarily suspended).

Other:

often – asthenic syndrome; possibly - accidental trauma, anemia, chest pain, diabetes mellitus, ecchymosis, influenza-like syndrome, periodontal abscess.

special instructions

Use with caution in the presence of risk factors for the development of rhabdomyolysis (including renal failure, hypothyroidism, personal or family history of hereditary muscle diseases and a previous history of muscle toxicity when using other HMG-CoA reductase inhibitors or fibrates), in chronic alcoholism, in older patients 65 years old, with a history of liver disease, sepsis, arterial hypotension, during major surgery, trauma, severe metabolic endocrine or electrolyte disturbances, with uncontrolled epilepsy, in people of Asian origin (Chinese, Japanese).

Therapy should be discontinued if CPK levels are significantly increased (more than 5 times the ULN) or if muscle symptoms are severe and cause daily discomfort (even if the CPK level is 5 times less than the ULN).

When using rosuvastatin at a dose of 40 mg, it is recommended to monitor renal function indicators.

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

An increased incidence of myositis and myopathy has been reported in patients taking other HMG-CoA reductase inhibitors in combination with fibric acid derivatives (including gemfibrozil), cyclosporine, niacin, azole antifungals, protease inhibitors and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when combined with certain HMG-CoA reductase inhibitors. Therefore, co-administration of rosuvastatin and gemfibrozil is not recommended. The balance of risk and possible benefit should be carefully weighed when using rosuvastatin and fibrates or niacin together.

It is recommended to determine liver function indicators before starting therapy and 3 months after starting therapy. The use of rosuvastatin should be discontinued or the dose reduced if the level of transaminase activity in the serum is 3 times higher than the ULN.

In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, treatment of underlying diseases should be carried out before starting treatment with rosuvastatin.
Impact on the ability to drive vehicles and operate machinery
When engaging in potentially hazardous activities, patients should take into account that dizziness may occur during therapy.

Use during pregnancy and breastfeeding

Restrictions during pregnancy - Contraindicated. Restrictions when breastfeeding - Contraindicated.

Contraindicated during pregnancy and lactation.

Do not use in women of reproductive age who do not use reliable methods of contraception.

Use for renal impairment

Restrictions for impaired renal function - Contraindicated.

Contraindicated in cases of severe renal impairment (creatinine clearance<30 ml/min).

Use for liver dysfunction

Restrictions for liver dysfunction - Contraindicated.

Contraindicated in active liver disease (including a persistent increase in liver transaminase activity or any increase in transaminase activity by more than 3 times compared to ULN).

Use in children

Restrictions for children - Contraindicated.

Contraindicated in children and adolescents under 18 years of age (since efficacy and safety have not been established).

Instructions for use of Rosuvastatin

The dosage is selected by the attending physician depending on the severity of the lipid profile disorder and the presence of cardiovascular risk.

The starting dose is 10 mg per day. If necessary, it is possible to increase the amount of the drug taken to 20 or 40 milligrams, but not earlier than after the start of treatment.

Increasing the daily dosage is possible only under the strict supervision of a specialist.

The drug should be taken whole, without chewing and with a sufficient amount of water. It is advisable to take the medication before meals.

Analogues of the drug

The drug has a fairly large number of analogues. Their cost can be both higher and lower and varies from 100 to 1000 rubles.

The most well-known analogues of Rosuvastatin include: Pravastatin, Lipitor, Simvastol, Lovastatin, Rozulip, Simvastatin, Atoris, Roxera, Crestor and a number of other drugs.

It is not recommended to change one medicine to another without the consent of a specialist. If necessary, the doctor himself will adjust the treatment, change the dosage and prescribe another drug.

Rosuvastatin, 30 pcs., 10 mg, film-coated tablets

Transport protein inhibitors

Rosuvastatin binds to some transport proteins, in particular OATP1B1 and BCRP. Concomitant use of drugs that are inhibitors of transport proteins may be accompanied by an increase in the concentration of rosuvastatin in the blood plasma and an increased risk of developing myopathy.

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. Does not affect plasma concentrations of cyclosporine. The drug Rosuvastatin is contraindicated in patients taking cyclosporine (see section "Contraindications").

Indirect anticoagulants: Initiating rosuvastatin therapy or increasing the dose of the drug in patients receiving concomitant vitamin K antagonists (for example, warfarin) may lead to an increase in prothrombin time (International Normalized Ratio - INR). Discontinuation of rosuvastatin or reduction of the drug dose may lead to a decrease in INR. In such cases, INR monitoring is recommended.

Gemfibrozil and other lipid-lowering drugs: the combined use of rosuvastatin and gemfibrozil leads to a 2-fold increase in the maximum concentration of rosuvastatin in blood plasma and the AUC of rosuvastatin. Based on specific interaction data, a pharmacokinetically significant interaction with fenofibrate is not expected, but a pharmacodynamic interaction is possible.

Gemfibrozil, fenofibrate, other fibrates and lipid-lowering doses of nicotinic acid (more than 1 g/day) increased the risk of myopathy when used concomitantly with HMG-CoA reductase inhibitors, possibly due to the fact that they can cause myopathy when used in monotherapy. When taking the drug simultaneously with gemfibrozil, fibrates, nicotinic acid in lipid-lowering doses (more than 1 g/day), an initial dose of the drug of 5 mg is recommended for patients; taking a dose of 40 mg is contraindicated when prescribed simultaneously with fibrates (see section “Contraindications”).

Ezetimibe: Concomitant use of rosuvastatin 10 mg and ezetimibe 10 mg was associated with an increase in rosuvastatin AUC in patients with hypercholesterolemia (see Table 3). An increased risk of side effects due to the pharmacodynamic interaction between Rosuvastatin and ezetimibe cannot be excluded.

HIV (human immunodeficiency virus) protease inhibitors: Although the exact mechanism of interaction is unknown, coadministration of HIV protease inhibitors may result in a significant increase in rosuvastatin exposure (see Table 3). Concomitant use of rosuvastatin and HIV protease inhibitors when treating patients with HIV is not recommended.

Antacids: simultaneous use of rosuvastatin and antacid suspensions containing aluminum and magnesium hydroxide leads to a decrease in plasma concentrations of rosuvastatin by approximately 50%. This effect is less pronounced if antacids are used 2 hours after taking rosuvastatin. The clinical significance of this interaction has not been studied.

Erythromycin: simultaneous use of rosuvastatin and erythromycin leads to a decrease in AUC of rosuvastatin by 20% and Cmax of rosuvastatin by 30%. This interaction may occur as a result of increased intestinal motility caused by erythromycin.

Oral contraceptives/hormone replacement therapy: Concomitant use of rosuvastatin and oral contraceptives increases the AUC of ethinyl estradiol and AUC of norgestrel by 26% and 34%, respectively. This increase in plasma concentration should be taken into account when selecting the dose of oral contraceptives. There are no pharmacokinetic data on the simultaneous use of Rosuvastatin and hormone replacement therapy; therefore, a similar effect cannot be excluded when using this combination. However, this combination was widely used during clinical trials and was well tolerated by patients.

Other medicinal products: No clinically significant interaction between rosuvastatin and digoxin is expected.

Cytochrome P450 isoenzymes: 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 weak substrate for these isoenzymes. Therefore, interaction of rosuvastatin with other drugs at the metabolic level involving cytochrome P450 isoenzymes is not expected.

There was no clinically significant interaction between rosuvastatin and fluconazole (an inhibitor of the CYP2C9 and CYP3A4 isoenzymes) and ketoconazole (an inhibitor of the CYP2A6 CYP3A4 isoenzymes).

Drug interactions that require rosuvastatin dose adjustment (see Table 1)

The dose of Rosuvastatin should be adjusted if it is necessary to use it simultaneously with drugs that increase exposure to rosuvastatin. If an increase in exposure by 2 times or more is expected, the initial dose of Rosuvastatin should be 5 mg 1 time per 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 that interact with rosuvastatin. For example, the maximum daily dose of Rosuvastatin when used simultaneously with gemfibrozil is 20 mg (increased exposure by 1.9 times), with ritonavir/atazanavir - 10 mg (increased exposure by 3.1 times).

Table 1. Effect of concomitant therapy on exposure to rosuvastatin (AUC, data are given in descending order)