Owencore
Effective both as monotherapy and in combination with bile acid sequestrants.
Before and during the course of treatment, the patient should be on a cholesterol-lowering diet.
If you miss the current dose, the drug must be taken as soon as possible. If it is time for the next dose, do not double the dose.
Before starting treatment, it is necessary to conduct a liver function test (monitor the activity of “liver” transaminases every 6 weeks for the first 3 months, then every 8 weeks for the remaining first year and then once every six months). For patients receiving simvastatin at a daily dose of 80 mg, liver function is monitored once every 3 months. In cases where the activity of “liver” transaminases increases (exceeding 3 times the upper limit of normal), treatment is canceled.
In patients with myalgia, myasthenia gravis and/or with a marked increase in CPK activity, treatment with the drug is discontinued.
Simvastatin (like other HMG-CoA reductase inhibitors) should not be used if there is an increased risk of rhabdomyolysis and renal failure (due to severe acute infection, hypotension, major surgery, trauma, severe metabolic disorders).
Cancellation of lipid-lowering drugs during pregnancy does not have a significant effect on the results of long-term treatment of primary hypercholesterolemia.
Due to the fact that HMG-CoA reductase inhibitors inhibit cholesterol synthesis, and cholesterol and other products of its synthesis play a significant role in fetal development, including the synthesis of steroids and cell membranes, simvastatin may have adverse effects on the fetus when administered to pregnant women ( Women of reproductive age should carefully follow contraceptive measures). If pregnancy occurs during treatment, the drug should be discontinued and the woman warned of the possible danger to the fetus.
There are no data regarding the excretion of simvastatin in women's breast milk, so breastfeeding should be discontinued.
There are no well-controlled studies for use in children. Some studies have shown effectiveness and good tolerability when used in children with severe cases of hypercholesterolemia. However, when using HMG-CoA reductase inhibitors in children under 18 years of age (and especially under 10 years of age), special caution should be exercised (given the importance of cholesterol in the growing body).
The drug is not indicated in cases where there is hypertriglyceridemia types I, V.
In patients with severe renal failure, treatment is carried out under the monitoring of renal function.
Patients are advised to immediately report unexplained muscle pain, lethargy, or weakness, especially if accompanied by malaise or fever.
Animal experiments revealed carcinogenic effects on the liver, lungs, thyroid gland, decreased fertility, degeneration of the vas deferens, testicular atrophy, and inhibition of spermatogenesis.
Ovencor, 10 mg, film-coated tablets, 30 pcs.
Before and during treatment with Ovencor, the patient should be on a cholesterol-lowering diet.
If you miss the current dose, the drug must be taken as soon as possible. If it is time to take the next dose, do not double the dose.
The duration of use of the drug Ovencor is determined by the attending physician individually.
Before starting therapy
Before starting or increasing the dose of Ovencor, the patient should be informed about the possibility of developing myopathy and should be advised to immediately consult a doctor if unexplained muscle pain, muscle hypersensitivity or muscle weakness occurs.
The drug should be used with caution in patients with predisposing factors for the development of rhabdomyolysis. In order to establish reference baseline values, CPK activity should be determined before starting treatment in the following situations:
— old age (over 65 years);
- female;
- renal dysfunction;
- uncontrolled hypothyroidism;
- personal or family history of congenital muscle pathology;
- history of muscle toxicity when using statins or fibrates;
- alcohol abuse.
Myopathy/rhabdomyolysis
Treatment with Ovencor may cause myopathy, which manifests itself as muscle pain, soreness or weakness and is accompanied by an increase in CPK activity (more than 10 times the upper limit of normal (ULN)). Myopathy may manifest itself in the form of rhabdomyolysis, sometimes accompanied by secondary acute renal failure due to myoglobinuria. In rare cases, death has occurred. The risk of developing myopathy increases with increasing plasma concentrations of substances that have an inhibitory effect on HMG-CoA reductase. Risk factors for developing myopathy include older age (65 years or older), female gender, uncontrolled hypothyroidism, and impaired renal function.
As with treatment with other HMG-CoA reductase inhibitors, the risk of developing myopathy/rhabdomyolysis is dose dependent. In clinical studies of simvastatin (median follow-up of 4 years), the incidence of myopathy at doses of 20 mg, 40 mg and 80 mg per day was 0.03%, 0.08% and 0.61%, respectively. In these studies, patients were closely monitored and a number of drugs that may interact with simvastatin were not used.
In patients taking Ovencor at a dose of 80 mg per day, the risk of developing myopathy is higher than when using other statins that cause a comparable decrease in LDL-C concentrations. Therefore, the drug Ovencor at a dose of 80 mg per day is recommended to be prescribed only to patients with a high risk of cardiovascular complications, in whom therapy with the drug at lower doses did not allow achieving target lipid concentrations, and the expected benefit of therapy outweighs the possible risk. If a patient taking Ovencor at a dose of 80 mg requires treatment with another drug that may interact with simvastatin, then it is necessary to reduce the dose of Ovencor or prescribe another statin that has less potential for possible drug interactions (see sections “Contraindications”, “Method” application and dose").
All patients starting therapy with Ovencor, as well as patients who need to increase the dose of the drug, should be warned about the possibility of myopathy and the need to immediately consult a doctor if unexplained pain, muscle soreness, lethargy or muscle weakness occurs, especially if accompanied by malaise or fever. Drug therapy should be discontinued immediately if myopathy is diagnosed or suspected.
The presence of the above symptoms and/or a more than 10-fold increase in CPK activity compared to ULN indicates the presence of myopathy. In most cases, after immediate discontinuation of Ovencor, the symptoms of myopathy resolve and CPK activity decreases. In patients starting to take Ovencor or switching to increased doses of the drug, periodic determination of CPK activity is advisable, but there is no guarantee that such monitoring can prevent the development of myopathy.
Ovencor, like other HMG-Co-A reductase inhibitors, should not be used if there is an increased risk of rhabdomyolysis and renal failure (due to severe acute infection, arterial hypotension, planned major surgery, trauma, severe metabolic disorders).
Therapy with Ovencor should be temporarily discontinued several days before major surgical interventions, as well as in the postoperative period.
The risk of developing myopathy/rhabdomyolysis increases when Ovencor is used concomitantly with the following drugs
Contraindicated drug combinations
Potent inhibitors of the CYP3A4 isoenzyme. Concomitant therapy with potent inhibitors of the CYP3A4 isoenzyme in therapeutic doses (for example, itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, drugs containing cobicistat) is contraindicated. If short-term treatment with potent inhibitors of the CYP3A4 isoenzyme cannot be avoided, therapy with Ovencor should be interrupted for the period of their use (see sections “Contraindications”, “Interaction with other drugs”).
– Gemfibrozil, cyclosporine or danazol.
The simultaneous use of these drugs with Ovencor is contraindicated (see sections “Contraindications”, “Interaction with other drugs”).
Other medicines
– Other fibrates.
In patients taking fibrates other than gemfibrozil (see section "Contraindications") or fenofibrate, the dose of simvastatin should not exceed 10 mg per day. With simultaneous use of simvastatin and fenofibrate, the risk of developing myopathy does not exceed the sum of the risks when treated with each drug separately. Simvastatin should be used with fenofibrate with caution, as both drugs can cause the development of myopathy. The addition of fibrate therapy to simvastatin therapy usually leads to a slight additional decrease in LDL-C concentrations, but allows for a more pronounced decrease in TG concentrations and an increase in HDL-C concentrations.
– Amiodarone.
In patients taking amiodarone, the dose of Ovencor should not exceed 20 mg per day (see section “Interaction with other drugs”).
– Blockers of “slow” calcium channels.
In patients taking verapamil, diltiazem or amlodipine, the dose of Ovencor should not exceed 20 mg per day (see section “Interaction with other drugs”).
- Lomitapide.
In patients with homozygous familial hypercholesterolemia taking lomitapide, the dose of Ovencor should not exceed 40 mg per day (see section “Interaction with other drugs”).
– Moderate inhibitors of the CYP3A4 isoenzyme.
With simultaneous use of drugs with moderate inhibitory activity against the CYP3A4 isoenzyme and simvastatin, especially at higher doses, the risk of developing myopathy may increase. When simvastatin is used concomitantly with moderate inhibitors of the CYP3A4 isoenzyme, a dose adjustment of simvastatin may be required.
– Fusidic acid.
Concomitant use of fusidic acid and simvastatin may increase the risk of developing myopathy (see section "Interaction with other drugs"). The simultaneous use of simvastatin and fusidic acid is not recommended. If the use of systemic fusidic acid preparations is considered necessary, Ovencor should be discontinued during this therapy. In exceptional cases, when long-term therapy with systemic fusidic acid is necessary, for example, for the treatment of severe infections, the possibility of simultaneous use of Ovencor and fusidic acid should be considered individually in each individual case and combination therapy should be carried out under close medical supervision.
– Nicotinic acid in lipid-lowering doses (more than 1 g/day).
When used simultaneously with nicotinic acid in lipid-lowering doses (more than 1 g/day), cases of myopathy/rhabdomyolysis have been described. The simultaneous use of simvastatin with nicotinic acid in lipid-lowering doses in patients of the Mongoloid race is not recommended, since the incidence of myopathy is higher in patients of Chinese nationality than in patients of other nationalities.
The risk of developing myopathy also increases in patients with severe renal failure.
Effect on the liver
At the beginning of therapy with Ovencor, a transient increase in the activity of liver enzymes is possible. When therapy with Ovencor is discontinued or interrupted, the activity of liver enzymes gradually returns to its original level. Increased activity of liver enzymes is usually not associated with jaundice or other clinical symptoms. No hypersensitivity reactions were identified.
Before starting therapy, and then in accordance with clinical indications, liver function tests are recommended in all patients. For patients who are planning to increase the dose of Ovencor to 80 mg per day, additional liver function tests should be performed before starting the indicated dosage, then every 3 months after starting its use, and then repeat regularly (for example, once every six months) during the first year of therapy.
Particular attention should be paid to patients with increased activity of liver enzymes. These patients need to repeat liver function tests in the near future and regularly thereafter until the activity of liver enzymes normalizes. If there is a persistent increase in transaminase activity (3 times compared to the initial level), Ovencor should be discontinued. The cause of increased alanine aminotransferase (ALT) activity may be muscle damage, so increased ALT and CPK activity may indicate the development of myopathy.
There are rare reports of fatal and non-fatal cases of liver failure in patients taking statins, including simvastatin. If severe liver damage with clinical symptoms and/or hyperbilirubinemia or jaundice develops during therapy with Ovencor, therapy should be discontinued immediately. If no other cause for the development of this pathology has been identified, repeated use of Ovencor is contraindicated.
In patients who abuse alcohol and/or patients with impaired liver function, the drug should be used with caution. Active liver disease or an unexplained increase in the activity of liver transaminases are contraindications to the use of Ovencor.
During treatment with Ovencor, as with treatment with other lipid-lowering drugs, a moderate (less than 3 times the ULN) increase in the activity of “liver” transaminases is possible. These changes appear soon after the start of treatment, are often transient, are not accompanied by any symptoms and do not require discontinuation of treatment.
Ophthalmological examination
Data from modern long-term clinical studies do not contain information regarding the adverse effects of simvastatin on the human lens.
Use in children and adolescents aged 10–17 years
The safety and effectiveness of simvastatin was studied in children and adolescents aged 10–17 years with heterozygous familial hypercholesterolemia: in boys 10–17 years old and girls 10–17 years old at least 1 year after menarche. In pediatric patients, the adverse event profile was comparable to that of patients receiving placebo. The use of simvastatin at a dose of more than 40 mg per day has not been studied in pediatric and adolescent patients. There was no significant effect of simvastatin use on the growth and puberty of boys and girls, or any effect on the duration of the menstrual cycle in girls. Girls should be advised about proper contraceptive methods during treatment with the drug. The use of simvastatin has not been studied in children under 10 years of age or in girls 10–17 years of age before menarche.
Use in elderly patients
In patients over the age of 65 years, the effectiveness of simvastatin, assessed by the level of reduction in the concentration of total cholesterol and LDL-C, was similar to the effectiveness observed in the population as a whole. There was no significant increase in the frequency of adverse events or changes in laboratory parameters. However, in a clinical study with simvastatin 80 mg daily in patients over 65 years of age, there was an increased risk of developing myopathy compared with patients under 65 years of age.
Renal dysfunction
In patients with severe renal failure (creatinine clearance less than 30 ml/min), treatment is carried out under the monitoring of renal function.
Diabetes
There are reports of increased plasma glucose concentrations when taking statins (see section "Side effects"), and in some patients predisposed to the development of diabetes mellitus, they can cause hyperglycemia. However, this risk does not outweigh the benefit from the therapeutic effect of statins - a reduction in the risk of developing cardiovascular diseases, and therefore is not a reason to stop taking statins. Patients predisposed to the development of diabetes mellitus (fasting glucose concentration 5.6–6.9 mmol/l, body mass index more than 30 kg/m2, increased TG concentration, arterial hypertension) should regularly monitor biochemical blood parameters and undergo clinical examination.
Interstitial lung disease
Cases of interstitial lung disease have been reported with the use of statins, especially with long-term use (see section "Side effects"). If patients develop symptoms of lung damage (shortness of breath, nonproductive cough) against the background of general symptoms (fatigue, weight loss, fever), it is necessary to stop taking the drug and consult a specialist.
Patients with rare hereditary diseases
For patients with rare hereditary diseases, such as lactose intolerance, lactose deficiency or glucose-galactose malabsorption, the use of Ovencor is contraindicated (see section "Contraindications").
Cancellation of lipid-lowering drugs during pregnancy does not have a significant effect on the results of long-term treatment of primary hypercholesterolemia.
Due to the fact that HMG-CoA reductase inhibitors inhibit cholesterol synthesis, and cholesterol and other products of its synthesis play a significant role in fetal development, including the synthesis of steroids and cell membranes, simvastatin may have adverse effects on the fetus when administered to pregnant women (women reproductive age should avoid conception). If pregnancy occurs during treatment, the drug should be discontinued and the woman warned of the possible danger to the fetus.
The use of Ovencor is not recommended in women of childbearing age who do not use contraceptives.
In patients with persistently elevated serum transaminase levels (exceeding 3 times the upper limit of normal), the drug should be discontinued.
Impact on the ability to drive vehicles and operate machinery
The drug Ovencor does not have or has an insignificant effect on the ability to drive vehicles and operate machinery. However, it should be borne in mind that isolated cases of dizziness have been reported during post-registration use of simvastatin.
