Ovenkor
Myopathy/rhabdomyolysis
Simvastatin, like other HMG-CoA reductase inhibitors, in rare cases causes myopathy, the symptoms of which are muscle pain, soreness or weakness in combination with an increase in creatine phosphokinase (CPK) activity more than 10 times the upper limit of normal (ULN) . Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure due to myoglobinuria, in very rare cases with death. The risk of myopathy increases with increasing levels of HMG-CoA reductase inhibitory activity in the blood plasma (in particular, with increasing levels of simvastatin or simvastatin hydroxy acid in the blood plasma), which may be due in part to drugs that enter into drug interactions and, as a result, affect on the metabolism and/or transporters of simvastatin (see section “Interaction with other drugs”).
As with other HMG-CoA reductase inhibitors, the risk of myopathy/rhabdomyolysis is dose dependent. In a clinical trial database of 41,413 patients receiving simvastatin, the incidence of myopathy was approximately 0.03%, 0.08%, and 0.61% with simvastatin doses of 20, 40, and 80 mg/day, respectively.
In a clinical trial in which patients with a history of myocardial infarction received simvastatin 80 mg/day (mean follow-up 6.7 years), the incidence of myopathy was approximately 1.0% compared with 0.02% in patients receiving drug at a dose of 20 mg/day. In approximately half of these cases, myopathy developed during the first year of treatment. The incidence of myopathy during each subsequent year of treatment was approximately 0.1% (see “Pharmacodynamics” and “Side Effects”).
Patients receiving simvastatin 80 mg are at higher risk of developing myopathy than other statin-based therapies with similar LDL-C lowering efficacy. Therefore, simvastatin 80 mg should be used only in patients with severe hypercholesterolemia and high risk of cardiovascular events who have not achieved treatment goals at lower doses and the expected benefits outweigh the potential risks.
In patients receiving simvastatin 80 mg and requiring another drug that may have a drug interaction, a lower dose of simvastatin or an alternative regimen using another statin with less potential for drug interactions should be used (see Interventions) . reducing the risk of myopathy caused by drug interactions
and sections “Method of administration and dosage”; "Contraindications"; "Interaction with other drugs").
In a clinical trial in which patients at high risk of cardiovascular disease received simvastatin 40 mg/day, the incidence of myopathy was approximately 0.05% in non-Chinese patients (n = 7367) compared with 0.24% in Chinese patients (n = 5468). Although the only Mongoloid population evaluated in this clinical study was the Chinese, caution should be exercised when prescribing simvastatin to Mongoloid patients and use the lowest dose necessary.
Decreased function of transport proteins
Decreased function of the liver OATP transport proteins may lead to increased systemic exposure of the hydroxy acid simvastatin and an increased risk of myopathy and rhabdomyolysis. A decrease in function may develop due to inhibition by drugs that interact with drugs (for example, cyclosporine), or in patients who are carriers of the c.521T>C polymorphism of the SLCO1B1 gene.
Patients with the c.521T>C allelic variant of the SLCO1B1 gene produce a less active OATP1B1 protein, and there is an increase in systemic exposure to the hydroxy acid simvastatin and an increased risk of myopathy. The risk of developing myopathy associated with high-dose simvastatin (80 mg) is generally 1% in the absence of genetic testing. Based on the results of the SEARCH study, carriers of the homozygous C allele (CC) who received 80 mg of the drug had a 15% risk of developing myopathy within a year, while in carriers of the heterozygous C allele (CT) the risk was 1.5%. The corresponding risk in patients with the most common genotype (TT) was 0.3% (see Pharmacokinetics). Whenever possible, genotyping for the presence of the C allele should be considered as part of the benefit-risk assessment before prescribing simvastatin 80 mg in individual patients, and high doses should be avoided in carriers of the CC genotype. At the same time, the absence of this gene during genotyping does not exclude the likelihood of developing myopathy.
Assessment of creatine phosphokinase activity
Assessment of creatine phosphokinase (CPK) activity should not be performed after intense exercise or when there is any plausible alternative cause for increased CPK activity, as this makes interpretation of the values difficult. If CK activity at baseline was significantly elevated (>5 x ULN), it should be assessed after 5-7 days to confirm the results.
Before treatment
When initiating or increasing the dose of simvastatin, all patients should be warned of the risk of myopathy and to promptly report any unexplained pain, tenderness, or muscle weakness.
Caution should be exercised when prescribing the drug to patients with predisposing factors to the development of rhabdomyolysis. In the following situations, CPK activity should be assessed before starting therapy in order to determine reference baseline values:
— old age (> 65 years);
- female;
- renal dysfunction;
- uncontrolled hypothyroidism;
— the patient’s or family history of hereditary muscle diseases;
- history of toxic effects of statins or fibrates on muscles;
- alcohol abuse.
In such situations, the benefit-risk ratio of treatment should be assessed, and clinical observation is recommended. If the patient has previously experienced muscle damage during fibrate or statin therapy, another drug in these classes can be prescribed only with caution. If there is a significant initial increase in CPK activity (> 5 x ULN), treatment should not be started.
During treatment
If pain, muscle weakness or cramps occur during statin therapy, CPK activity should be assessed. If a significant increase in CK activity is detected (> 5 x ULN) in the absence of intense physical activity, treatment should be discontinued. If muscle symptoms are severe and cause daily discomfort, discontinuation of treatment may be considered, even if there is no increase in CPK activity <5 x ULN. If myopathy is suspected for any other reason, treatment should be discontinued.
There are very rare reports of immune-mediated necrotizing myopathy (IONM) during or after treatment with certain statins. Clinically, IONM is characterized by persistent proximal muscle weakness and increased serum creatine phosphokinase activity, which persists despite cessation of statin therapy (see “Side Effects”).
If symptoms resolve and CPK activity returns to normal, consideration may be given to resuming statin therapy or to prescribing another statin at a minimal dose under close monitoring.
A higher incidence of myopathy was observed in patients in whom the dose was increased to 80 mg (see Pharmacodynamics). Periodic assessment of CPK activity is recommended, as this may be useful in identifying subclinical cases of myopathy. At the same time, there is no certainty that such control will prevent the development of myopathy.
Simvastatin therapy should be temporarily discontinued several days before major elective surgery and when severe conditions requiring medical or surgical intervention develop.
Measures to reduce the risk of myopathy caused by drug interactions (see “Interactions with other drugs”)
The risk of myopathy and rhabdomyolysis increases significantly when simvastatin is co-administered with strong CYP3A4 inhibitors such as itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors (eg, nelfinavir), boceprevir, telaprevir, nefazodone, drugs containing cobicistat, as well as gemfibrozil, cyclosporine and danazol. The use of these drugs together with simvastatin is contraindicated (see "Contraindications").
The risk of developing myopathy and rhabdomyolysis also increases with simultaneous use of amiodarone, amlodipine, verapamil or diltiazem with certain doses of simvastatin (see "Dosage and Administration"; "Interaction with other drugs"). The risk of myopathy, including rhabdomyolysis, may be increased with concomitant use of fusidic acid and statins (see Interactions with Other Drugs). In patients with homozygous familial hypercholesterolemia, this risk may be increased when lomitapide is used concomitantly with simvastatin.
Therefore, with regard to CYP3A4 inhibitors, the use of simvastatin with itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors (eg, nelfinavir), boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone and medicinal products containing cobicistat is contraindicated (see section 4.4). “Contraindications”; “Interaction with other drugs”). If the use of strong CYP3A4 inhibitors (drugs that increase AUC by approximately 5-fold or greater) cannot be avoided, simvastatin therapy should be temporarily discontinued (and a different statin considered) for the duration of treatment. Moreover, caution must be exercised when combining simvastatin with other less potent CYP3A4 inhibitors: fluconazole, verapamil, diltiazem (see "Dosage and Administration"; "Interaction with other drugs"). The simultaneous use of simvastatin and grapefruit juice should be avoided.
The simultaneous use of simvastatin and gemfibrozil is contraindicated (see "Contraindications"). Due to the increased risk of myopathy and rhabdomyolysis in patients receiving simvastatin together with other fibrates, with the exception of fenofibrate, the dose of simvastatin should not exceed 10 mg per day (see "Dosage and Administration"; "Interactions with other drugs"). Caution should be exercised when prescribing fenofibrate and simvastatin, since each of these drugs itself can cause the development of myopathy. Simvastatin should not be co-administered with systemic fusidic acid or used within 7 days of finishing treatment with fusidic acid. If the use of fusidic acid is necessary, statin therapy should be suspended for the entire period of fusidic acid treatment. There are reports of cases of rhabdomyolysis (including fatal cases) in patients receiving a combination of fusidic acid and statins (see “Interactions with other drugs”). The patient should be advised to consult a doctor immediately if any symptoms such as pain, tenderness or muscle weakness develop. Statin therapy can be resumed seven days after the last fusidic acid dose. In exceptional situations where long-term systemic therapy with fusidic acid is necessary, for example in severe infections, the advisability of simultaneous use of simvastatin and fusidic acid should be assessed on a case-by-case basis and under close medical supervision.
The combined use of simvastatin in doses exceeding 20 mg per day with amiodarone, amlodipine, verapamil or diltiazem should be avoided. In patients with homozygous familial hypercholesterolemia, the combined use of simvastatin in doses exceeding 40 mg per day with lomitapide should be avoided (see "Dosage and Administration"; "Contraindications"; "Interaction with other drugs").
Patients taking other medicinal products with moderate inhibitory effects on CYP3A4 concomitantly with high-dose simvastatin may have an increased risk of developing myopathy. When simvastatin is used concomitantly with moderate CYP3A4 inhibitors (drugs that increase AUC by approximately 2-5 times), a dose adjustment of simvastatin may be required. For some moderate CYP3A4 inhibitors, such as diltiazem, the maximum recommended dose of simvastatin is 20 mg (see Dosage and Administration).
Simvastatin is a substrate of the Breast Cancer Resistant Protein (BCRP) efflux transporter. Concomitant use of drugs that are BCRP inhibitors (such as elbasvir and grazoprevir) may lead to increased plasma concentrations of simvastatin and an increased risk of myopathy. Therefore, consideration should be given to adjusting the dose of simvastatin depending on the prescribed dose. Concomitant use of elbasvir and grazoprevir with simvastatin has not been studied; in patients who simultaneously receive drugs containing elbasvir and grazoprevir and simvastatin, the dose of simvastatin should not exceed 20 mg per day (see “Interactions with other drugs”).
Rare cases of myopathy/rhabdomyolysis have been associated with the concomitant use of HMG-CoA reductase inhibitors and lipid-lowering doses (≥ 1 g/day) of niacin (nicotinic acid), each of which alone can cause myopathy.
In a clinical trial (median follow-up 3.9 years) involving patients at high risk of cardiovascular disease with well-controlled LDL-C levels, no additional benefit was found during therapy with simvastatin 40 mg/day with or without ezetimibe 10 mg. benefits on cardiovascular outcomes with the addition of niacin (niacin) at lipid-lowering doses (≥ 1 g/day).
Therefore, clinicians considering combination therapy with simvastatin with lipid-lowering doses (≥ 1 g/day) of niacin (nicotinic acid) or niacin-containing products should carefully weigh the potential benefits and risks and closely monitor patients for any signs and symptoms symptoms in the form of pain, soreness or weakness in the muscles, especially in the first months of therapy and when the dose of any of the drugs is increased.
Additionally, in this study, the incidence of myopathy was approximately 0.24% in Chinese patients receiving simvastatin 40 mg or ezetimibe/simvastatin 10/40 mg, compared with 1.24% in Chinese patients receiving simvastatin 40 mg or ezetimibe/simvastatin 10/40 mg together with nicotinic acid/lamopiprant modified release 2000 mg/40 mg. Although the only Mongoloid population evaluated in this clinical study was Chinese, given the higher incidence of myopathy in Chinese patients compared to non-Chinese patients, concomitant use of simvastatin with niacin (niacin) at lipid-lowering doses (≥ 1 g/day) It is not recommended for patients of the Mongoloid race (see “Interaction with other drugs”).
Acipimox is structurally related to niacin. Although acipimox has not been studied, the risk of muscle toxicity may be similar to that of niacin.
Effect on the liver
In clinical studies, persistent increases in serum transaminase activity (up to > 3 x ULN) were observed in a small number of adult patients receiving simvastatin. When simvastatin therapy was discontinued or temporarily discontinued in these patients, transaminase activity usually decreased slowly to the level observed before treatment.
It is recommended to assess liver function before starting treatment and then when clinically indicated. In patients whose dose was increased to 80 mg, liver function should be further assessed before the dose increase, 3 months thereafter, and periodically thereafter (eg, once every six months) during the first year of treatment. Particular attention should be paid to patients who experience increased transaminase activity in the blood serum. In such patients, liver function assessment should be repeated quickly and performed more frequently thereafter. If transaminase activity indicates progression of the condition, especially if it rises to 3 x ULN and persists, simvastatin should be discontinued. Please note that ALT activity may be due to damage to muscle tissue, so an increase in ALT activity in combination with an increase in CPK activity may indicate myopathy (see Myopathy/Rhabdomyolysis subsection).
There are limited post-marketing reports of fatal and non-fatal liver failure in patients treated with statins, including simvastatin. If serious liver damage develops during treatment with Ovencor, accompanied by clinical symptoms and/or hyperbilirubinemia or jaundice, therapy should be discontinued immediately. Unless another cause of liver damage has been established, therapy with Ovencor should not be resumed.
In patients who consume significant amounts of alcohol, the drug should be used with caution.
As with the use of other lipid-lowering drugs, cases of moderate (<3 x ULN) increases in serum transaminase activity have been described during simvastatin therapy. These changes occurred shortly after initiation of simvastatin therapy, were often transient, were not accompanied by any symptoms, and did not require interruption of treatment.
Diabetes
Some evidence suggests that statins as a class increase blood glucose concentrations, and in some patients at high risk of developing diabetes mellitus, statins may lead to a level of hyperglycemia at which glucose-lowering drugs should formally be prescribed. At the same time, this risk is outweighed by the reduction in vascular risk with statins and, therefore, should not be a reason to discontinue therapy. Patients at risk of developing diabetes mellitus (fasting glucose concentration 5.6 to 6.9 mmol/l, BMI > 30 kg/m2, elevated triglycerides, hypertension) should be monitored both clinically and biochemically in accordance with national guidelines.
Interstitial lung diseases
Cases of the development of interstitial lung disease have been described with the use of some statins, including simvastatin, especially with long-term therapy (see “Side effects”). Signs of interstitial lung disease include shortness of breath, nonproductive cough, and deterioration in general health (weakness, weight loss, and fever). If the development of interstitial lung disease is suspected, statin therapy should be discontinued.
Use in children and adolescents aged 10-17 years
The safety and effectiveness of simvastatin in adolescents aged 10–17 years with heterozygous familial hypercholesterolemia was assessed in a controlled clinical trial in adolescent boys with Tanner stage II or higher and girls who were at least one year postmenarche. Patients receiving simvastatin had an overall adverse event profile similar to that of patients receiving placebo. Doses above 40 mg have not been studied in this patient population. In this limited controlled study, there was no evidence of an effect of the drug on growth or puberty in adolescent girls and boys, or an effect on the duration of the menstrual cycle in girls (see “Pharmacodynamics”; “Dosage and Administration”; “Side Effects”) "). Adolescent girls should be advised of the need to use appropriate methods of contraception during therapy with simvastatin (see “Contraindications”; “Use during pregnancy and breastfeeding”). In patients aged <18 years, the efficacy and safety of the drug for treatment durations > 48 weeks is unknown, and long-term effects on physical, intellectual and pubertal maturation have not been studied. Studies on the use of simvastatin in patients under 10 years of age, as well as in prepubertal children and premenarchal girls, have not been conducted.
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.
