Simvastatin, 20 mg 20

How to take, the dosage

Prior to Simvastatin treatment, the patient should be prescribed a standard hypocholesterolemic diet, which should be followed during the entire course of treatment.

Simvastatin should be taken orally once a day in the evening, with plenty of water.
The time of taking the drug should not be associated with meals.

The recommended dose of Simvastatin for the treatment of hypercholesterolemia varies from 5 to 80 mg once a day in the evening.

The recommended initial dose of the drug for patients with hypercholesterolemia is 10 mg. The maximum daily dose is 80 mg.

The dose should be changed (adjusted) in 4 weeks intervals. In most patients the optimal effect is reached while taking the preparation in dose up to 20 mg per day.

In patients with homozygous hereditary hypercholesterolemia it is recommended to take Simvastatin daily dose of 40 mg once a day in the evening or 80 mg in three intakes (20 mg in the morning, 20 mg during the day and 40 mg in the evening).

When treating patients with coronary heart disease (CHD) or high risk of CHD, effective doses of Simvastatin are 20-40 mg daily.

Therefore recommended initial dose in such patients is 20 mg per day. The dose should be changed (adjusted) at intervals of 4 weeks and if necessary the dose may be increased up to 40 mg daily.

If LDL content is less than 75 mg/dl (1.94 mmol/l), total cholesterol content – less than 140 mg/dl (3.6 mmol/l), the drug dose should be reduced.

In elderly patients and in patients with mild or moderately expressed renal insufficiency the drug dosage should not be changed.

In patients with severe chronic renal insufficiency (creatinine clearance less than 30 ml/min) the maximum recommended dose of Simvastatin should not exceed 10 mg per day.

Administration in children and adolescents 10-17 years old with heterozygous familial hypercholesterolemia

The recommended initial dose is 10 mg daily in the evening. The recommended dosing regimen is 10-40 mg per day, the maximum recommended dose is 40 mg per day. The dosage is adjusted individually in accordance with the therapy goals.

Related therapy

Simvastatin is effective both as monotherapy and in combination with bile acid sequestrants (see section “Interaction with other medicinal products”).

In patients taking Simvastatin concomitantly with fibrates, except gemfibrozil (see section “Contraindications”) or fenofibrate, the maximum recommended dose of Simvastatin is 10 mg per day.

In concomitant use of the drug with dronedarone the dose of simvastatin should not exceed 10 mg per day.

In concomitant use of the drug with amiodarone, amlodipine, diltiazem, verapamil, ranolazine the dose of simvastatin should not exceed 20 mg per day.

In concomitant use of the drug with lomitapide daily dose of simvastatin should not exceed 40 mg (see section “Interaction with other medicinal products”).

Interaction

Contraindicated drug combinations

Concomitant therapy with the following drugs is contraindicated.

Strong inhibitors of CYP3A4 isoenzyme. Simvastatin is metabolized by CYP3A4 isoenzyme, but does not inhibit the activity of this isoenzyme.

This suggests that simvastatin administration has no effect on plasma concentrations of drugs metabolized by CYP3A4 isoenzyme.

Strong CYP3A4 isoenzyme inhibitors increase the risk of myopathy by reducing the excretion rate of simvastatin.

Concomitant use of strong CYP3A4 isoenzyme inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors,

boceprevir, telaprevir, nefazodone, drugs containing cobicistat) and simvastatin are contraindicated (see

Gemfibrozil, cyclosporine, or danazol (see Contraindications; Special Indications, Myopathy/Rhabdomyolysis).

Gemfibrozil, cyclosporine, or danazol.
(see Contraindications. Contraindications; Special Indications, Myopathy/Rhabdomyolysis).

Interaction with other drugs

Other fibrates. The risk of myopathy increases with concomitant use of simvastatin with gemfibrozil (see section “Contraindications”) and other fibrates (except fenofibrate).

These hypolipidemic agents can cause myopathy in monotherapy. When concomitant use of simvastatin with fenofibrate, the risk of myopathy did not exceed the sum of the risks when monotherapy with each drug is used (see sections “Contraindications”; “Special Precautions”, Myopathy/Rhabdomyolysis).

Amiodarone. Risk of myopathy/rhabdomyolysis increases with concomitant use of amiodarone with simvastatin. In clinical study incidence of myopathy in patients who concomitantly took

simvastatin in dose of 80 mg and amiodarone was 6% (see sections “Dosage and administration” and “Caution”, myopathy/rhabdomyolysis).

Slow calcium channel blockers. Risk of myopathy/rhabdomyolysis increases with concomitant use of verapamil, diltiazem or amlodipine with simvastatin (see sect. “Dosage and administration”; “Cautionary statements”, Myopathy/Rhabdomyolysis).

Lomitapide. Risk of myopathy/rhabdomyolysis may increase with concomitant use of lomitapide with simvastatin (see sect. “Dosage and administration”; “Cautionary statements”, Myopathy/Rhabdomyolysis).

Moderate CYP3A4 isoenzyme inhibitors (such as dronedarone). When concomitant use of drugs with moderate inhibitory activity against CYP3A4 isoenzyme and

simvastatin, especially in higher doses, the risk of myopathy may increase (see section “Cautions”, Myopathy/Rhabdomyolysis). In concomitant use of simvastatin with moderate CYP3A4 isoenzyme inhibitors, simvastatin dose reduction may be required.

Ranolazine (moderate CYP3A4 isoenzyme inhibitor). Concomitant use of ranolazine and simvastatin may increase the risk of myopathy (see section “Cautions”, Myopathy/Rhabdomyolysis).

Simultaneous use of simvastatin and ranolazine may require dose reduction of simvastatin.
OATP1B1 transport protein inhibitors. Hydroxy acid of simvastatin is a substrate of OATP1B1 transport protein.

Simultaneous use of OATP1B1 transport protein inhibitors and simvastatin may lead to increased plasma concentration of simvastatin hydroxy acid and increased risk of myopathy (see sections “Contraindications”; “Special Precautions”, Myopathy/Rhabdomyolysis).

Fusidic acid. In concomitant use of fusidic acid and simvastatin the risk of myopathy may increase (see section “Special Precautions”, Myopathy/Rhabdomyolysis).

Nicotinic acid (at least 1 g/day). In concomitant use of simvastatin and nicotinic acid in lipid-lowering doses (at least 1 g/day) cases of myopathy/rhabdomyolysis are described (see section “Special Precautions”, Myopathy/Rhabdomyolysis).

Colchicine. When concomitant use of colchicine and simvastatin in patients with renal insufficiency, cases of myopathy and rhabdomyolysis have been described. When combined therapy with these drugs these patients should be closely monitored.

Incompatible anticoagulants (coumarin derivatives). Simvastatin at a dose of 20-40 mg daily potentiates the effect of coumarin anticoagulants: prothrombin time, defined as the international normalized

ratio (INR), increases from baseline of 1.7 to 1.8 in healthy volunteers and from 2.6 to 3.4 in patients with hypercholesterolemia.

In patients taking coumarin anticoagulants, prothrombin time should be
determined before the start of therapy with simvastatin, and often enough during the initial treatment period to avoid significant changes in this indicator.

Once a stable INR value is achieved, its further determination should be carried out at intervals recommended for monitoring patients receiving anticoagulant therapy.

If the dose of simvastatin is changed or after its withdrawal, regular measurement of prothrombin time is also recommended.

In patients who have not taken anticoagulants, simvastatin therapy has not been associated with the occurrence of bleeding or changes in prothrombin time.

Digoxin. Increased plasma concentrations of digoxin may occur.

Bile acid sequestrants. Colestiramine and colestipol decrease bioavailability of simvastatin; simvastatin may be used 2 hours before or 4 hours after taking the above medicinal agents, and an additive effect is noted.

Other interactions

Grapefruit juice contains one or more components that inhibit CYP3A4 isoenzyme and may increase the plasma concentration of drugs metabolized by CYP3A4 isoenzyme.

When drinking juice in usual amount (1 cup 250 ml per day) this effect is minimal (there is a 13% increase of activity of HMG-CoA reductase inhibitors when estimated by AUC value) and has no clinical significance.

However, consumption of grapefruit juice in large volumes significantly increases the activity of HMG-CoA reductase inhibitors in blood plasma.

In this regard, consumption of grapefruit juice during simvastatin therapy should be avoided (see section “Special Precautions”, Myopathy/Rhabdomyolysis).

Special Instructions

Myopathy/Rhabdomyolysis

Simvastatin, like other statins, may cause myopathy, which is manifested by muscle pain, soreness or weakness and accompanied by increased CPK activity (more than 10 times the upper limit of normal (ULN)).

Myopathy may manifest as rhabdomyolysis, sometimes accompanied by secondary acute renal failure due to myoglobinuria.

In rare cases fatal outcome was observed. The risk of myopathy increases with the increase of plasma concentration of substances with inhibitory effect against HMG-CoA reductase.

Risk factors for myopathy include older age (65 years and older), female gender, uncontrolled hypothyroidism and impaired renal function.

As with treatment with other HMG-CoA reductase inhibitors, the risk of myopathy/rhabdomyolysis is dose dependent.

In clinical studies (median follow-up of 4 years) myopathy incidence was 0.03%, 0.08%, and 0.61% in doses of 20, 40, and 80 mg daily, respectively.

In these studies, patients were closely monitored and a number of drugs that may interact with simvastatin were not used.

In a clinical trial in which patients with a history of myocardial infarction were taking simvastatin at a dose of 80 mg daily (mean follow-up duration 6.7 years), the incidence of myopathy was approximately 1.0% and in patients taking simvastatin at a dose of 20 mg daily, 0.02%.

Approximately half of the cases of myopathy were reported during the first year of treatment. The incidence of myopathy during each subsequent year of treatment was approximately 0.1%.

Patients taking simvastatin at a dose of 80 mg daily had a higher risk of myopathy than other statins causing a comparable decrease in LDL cholesterol concentration.

Therefore, Simvastatin at a dose of 80 mg daily should be administered only to patients at high risk of cardiovascular complications in whom therapy with the drug at lower doses failed to achieve the desired therapeutic effect, and the expected benefit of treatment exceeds the possible risk.

If a patient taking Simvastatin at a dose of 80 mg requires treatment with another drug that may interact with Simvastatin, the dose of Simvastatin should be reduced or

another statin with less potential for possible drug interaction should be prescribed (see Sections “Contraindications”; “Administration and Doses”).

All patients who start therapy with Simvastatin, as well as patients who need to increase the dose, should be warned about the possibility of myopathy and informed about

the need to immediately consult a physician in case of any unexplained muscle pain, muscle soreness or muscle weakness.

Therapy with Simvastatin should be stopped immediately if myopathy is suspected or diagnosed.

The presence of the above symptoms and/or more than 10-fold increase in CPK activity compared to CHF indicates the presence of myopathy.

In most cases, after immediate discontinuation of simvastatin, myopathy symptoms resolve and CPK activity decreases.

In patients starting Simvastatin or switching to higher 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.

Many patients who underwent rhabdomyolysis during simvastatin therapy have a complicated history, including impaired renal function, usually due to diabetes mellitus. These patients require closer monitoring.

Simvastatin, as well as other HMG-CoA reductase inhibitors, should not be used with an increased risk of rhabdomyolysis and renal failure (against the background of severe acute infection, arterial hypotension, planned major surgery, trauma, severe metabolic disorders).

Therapy with Simvastatin should be temporarily discontinued a few days before major surgical interventions, as well as in the postoperative period.

In a clinical trial in which patients at high risk for cardiovascular disease took simvastatin at a dose of 40 mg once daily (median follow-up duration 3.9 years), the incidence of

myopathy was approximately 0.24% among patients of Chinese ethnicity (n=5468) and 0.05% among patients of other ethnicity (n=7367).

Although the only Chinese patients in this clinical trial were of mongoloid race, caution should be exercised when prescribing simvastatin to mongoloid patients, particularly prescribing it at low doses.

In carriers of the SLCO1B1*5 allelic variant (c.521T>C) of the SLCO1B1 gene, the activity of transport proteins that take up statins from the blood is reduced, which may lead to increased systemic exposure of

simvastatin and an increased risk of myopathy and rhabdomyolysis. In general population (without genetic testing) the risk of myopathy when using simvastatin at high dose (80 mg) is 1%.

According to the SEARCH study, homozygous carriers of the C (CC) allele who received simvastatin at a dose of 80 mg had a 15% risk of developing myopathy within one year, while heterozygous carriers of the C (CT) allele had a 1.5% risk of developing myopathy and carriers of the most frequent genotype (TT) had a 0.3% risk.

Before prescribing simvastatin at a dose of 80 mg, it is advisable to perform genotyping (as part of the benefit and risk assessment of therapy) to determine if the patient has the C allele.

Carriers of genotype CC should not be prescribed high doses of the drug. Keep in mind that the absence of this allele variant in genotyping does not exclude the possibility of myopathy development in the patient.

Risk of myopathy/rhabdomyolysis increases with concomitant use of Simvastatin with the following drugs.

Contraindicated combinations of drugs

– Strong inhibitors of CYP3A4 isoenzyme. Concomitant therapy with strong CYP3A4 isoenzyme inhibitors in therapeutic doses (e.g., itraconazole, ketoconazole, posaconazole, voriconazole,

erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone or preparations containing cobicistat) is contraindicated.

If short-term treatment with strong CYP3A4 isoenzyme inhibitors cannot be avoided, therapy with Simvastatin should be interrupted for the period of their use (see sections “Contraindications”; “Interaction with other medicinal products”).

– Gemfibrozil, cyclosporine or danazol. Simultaneous use of these drugs with the drug Simvastatin is contraindicated (see sections “Contraindications”; “Interaction with other medicinal products”).

Other drugs

– 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.

If simvastatin and fenofibrate are used concomitantly, the risk of myopathy does not exceed the sum of risks of treatment with each drug separately.

Fenofibrate in combination with simvastatin should be administered with caution because both drugs may cause myopathy.

The addition of fibrates therapy to simvastatin therapy usually leads to a small additional decrease in LDL cholesterol concentration, but allows a more pronounced decrease in TG concentration and increase in HDL cholesterol concentration.

In small short clinical trials in which both drugs were used under close supervision, combination therapy of fibrates with simvastatin was not accompanied by the development of myopathy (see section “Interaction with other medicinal products”).

– Amiodarone. In patients taking amiodarone the dose of simvastatin should not exceed 20 mg per day (see section “Interaction with other medicinal products”).

– Slow calcium channel blockers. In patients taking verapamil, diltiazem or amlodipine the dose of simvastatin should not exceed 20 mg per day (see section “Interaction with other medicinal products”).

– Lomitapide. In patients with homozygous familial hypercholesterolemia taking lomitapide, the dose of simvastatin should not exceed 40 mg per day (see section “Interaction with other medicinal products”).

– Moderate CYP3A4 isoenzyme inhibitors.

Simultaneous use of drugs with moderate inhibitory activity against CYP3A4 isoenzyme and simvastatin, especially in higher doses, may increase the risk of myopathy.

Simultaneous use of simvastatin with moderate CYP3A4 isoenzyme inhibitors may require correction of the dose of simvastatin.

– Fusidic acid. Concomitant use of fusidic acid and simvastatin may increase the risk of myopathy (see section “Interaction with other medicinal products”).

Simultaneous use of simvastatin and fusidic acid is not recommended. If the use of systemic agents of fusidic acid is considered necessary, Simvastatin should be discontinued for the period of this therapy.

In exceptional cases where prolonged therapy with systemic fusidic acid preparations is necessary, such as for the treatment of severe infections, the possibility of concomitant use of simvastatin and fusidic acid

should be considered on a case-by-case basis and the combination therapy should be conducted under close medical supervision.

– Nicotinic acid (in lipid-lowering doses of at least 1 g/day). When concomitant use of simvastatin and nicotinic acid in lipid-lowering doses (at least 1 g/day) there have been described cases of myopathy/rhabdomyolysis.

In a clinical trial (median duration of follow-up 3.9 years) involving patients with high cardiovascular risk and well-controlled LDL cholesterol concentrations using

simvastatin at a dose of 40 mg/day with or without ezetimibe 10 mg/day was shown to have no additional beneficial effect on cardiovascular outcomes with concomitant use of nicotinic acid in lipid-lowering doses (at least 1 g/day).

Thus, the benefit of concomitant use of simvastatin with nicotinic acid in lipid-lowering doses (at least 1 g/day) should be carefully weighed against the potential risks of combination therapy.

In addition, in this study, the incidence of myopathy was approximately 0.24% among Chinese patients when taking simvastatin at a dose of 40 mg or simvastatin/ezetimibe at a dose of 40/10 mg by

compared with 1.24% among Chinese patients when taking simvastatin at a dose of 40 mg or simvastatin/ezetimibe at a dose of 40/10 mg concomitantly with a 40 mg/2 g dose of laropiprant/nicotinic acid delayed-release.

Despite the fact that in this clinical trial the only Mongoloid patients were of Chinese ethnicity, concomitant use of simvastatin with

nicotinic acid in lipid-lowering doses (at least 1 g/day) in patients of mongoloid race is not recommended, because the incidence of myopathy is higher in patients of Chinese ethnicity than in patients of other ethnicities (see “Interaction with other nationalities.

Impact on the liver

In some adult patients who took simvastatin there was a steady increase in the activity of “hepatic” enzymes (more than 3 times the HGH).

Upon discontinuation or interruption of simvastatin therapy, the activity of “hepatic” transaminases usually gradually returned to the initial level.

Increased activity of “hepatic” transaminases was not associated with jaundice or other clinical symptomatology.

No hypersensitivity reactions were detected.

Some of the above patients had abnormal results of functional liver tests prior to treatment with simvastatin and/or abused alcohol.

Before treatment and then according to clinical indications all patients are recommended to perform liver function tests.

Patients in whom it is planned to increase the dose of simvastatin up to 80 mg per day should have additional liver function tests before proceeding to the specified dosage, then 3

months after the start of its use and then regularly repeated (for example, once every six months) during the first year of treatment. Particular attention should be paid to patients with increased activity of liver transaminases.

These patients should repeat liver function tests in the near future and thereafter regularly until normalization of the activity of “hepatic” transaminases.

In cases where the activity of “hepatic” transaminases increases, especially with a sustained 3-fold excess of HGH, the drug should be discontinued.

The cause of increased alanine aminotransferase (ALT) activity may be muscle damage, so the increase in ALT and CPK activity may indicate the development of myopathy (see section “Special Indications”, Myopathy/Rhabdomyolysis).

There have been rare post-registration reports of fatal and non-fatal cases of hepatic failure in patients taking statins, including simvastatin.

If during treatment with Simvastatin severe liver damage with clinical symptoms and/or hyperbilirubinemia or jaundice develops, therapy should be immediately discontinued.

If no other cause of this pathology has been identified, reapplication of simvastatin is contraindicated.

In patients who abuse alcohol and/or patients with impaired liver function, the drug should be used with special caution.

Active liver disease or unexplained increase in the activity of “hepatic” transaminases are contraindications for prescribing the drug.

During treatment with simvastatin, as well as during treatment with other hypolipidemic drugs, a moderate (exceeding BHN by less than 3 times) increase in “hepatic” transaminases activity was observed.

These changes appeared soon after the start of treatment, were often transient, were not accompanied by any symptoms and did not require interruption of treatment.

Ophthalmological examination

Data of modern long-term clinical studies contain no information regarding the adverse effects of simvastatin on the human eye lens.

Use in children and adolescents aged 10-17 years

The safety and efficacy of simvastatin in children and adolescents aged 10-17 years with heterozygous familial hypercholesterolemia have been evaluated in controlled clinical trials involving 10-17 year old boys and girls

10-17 years old at least 1 year after menarche. In pediatric patients taking simvastatin, the adverse event profile was comparable to that of patients taking placebo.

The use of simvastatin at a dose greater than 40 mg per day has not been studied in pediatric and adolescent patients.

In this study there was no observable effect of simvastatin administration on growth and puberty in boys and girls or any effect on the duration of menstrual cycle in girls.

Girls should be advised of appropriate contraceptive methods during treatment with Simvastatin (see Sections “Contraindications”; “Use during pregnancy and breastfeeding”).

The use of simvastatin has not been studied in children younger than 10 years and in girls 10-17 years before menarche.

Use in elderly patients

In patients over 65 years of age, the efficacy of simvastatin, as assessed by the level of reduction in total cholesterol and LDL concentrations, was similar to that observed in the general population.

No significant increase in the incidence of adverse events or changes in laboratory parameters was observed.

However, in a clinical study of simvastatin at a dose of 80 mg per day in patients over 65 years of age there was an increased risk of myopathy compared to patients younger than 65 years.

In order to diagnose the development of myopathy it is recommended to perform regular measurements of CPK.

During simvastatin treatment serum CPK content may increase, which should be considered in differential diagnosis of chest pain.

The criterion for discontinuation of the drug is increase of serum CPK content by more than 10 times compared to the upper limit of normal values.

In patients with myalgia, myasthenia and/or marked increase of CPK activity the drug is stopped.

In case the current dose is missed the drug should be taken as soon as possible. If it is time for the next dose, the dose should not be doubled.

Patients with severe renal insufficiency should be treated under monitoring of renal function.

In patients with reduced thyroid function (hypothyroidism) or with some renal diseases (nephrotic syndrome) when cholesterol levels increase should be first treated with therapy of the underlying disease.

The duration of drug administration is determined by the attending physician individually.

Effect on the ability to drive vehicles and operate mechanisms

No adverse effects of simvastatin on the ability to drive vehicles and operate mechanisms have been reported.

Contraindications

• High sensitivity to simvastatin or other drug components as well as to other statin drugs (HMG-CoA reductase inhibitors) in the history;
• Hepatic diseases in active phase, persistent increase in the activity of “hepatic transaminases” of unknown etiology.
• hepatic diseases in active phase, stable increase of “hepatic” transaminases activity of unknown etiology;
• diseases of skeletal muscles (myopathy);
• Disorders of skeletal musclesconcomitant use with strong CYP3A4 isoenzyme inhibitors (itraconazole, ketoconazole, voriconazole, posaconazole, HIV protease inhibitors, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone and drugs containing cobicistat);
• concomitant treatment with gemfibrozil, cyclosporine, or danazol;
• age less than 18 years (except children and adolescents 10-17 years with heterozygous familial hypercholesterolemia) (see
• Application during pregnancy and lactation
• Lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the drug contains lactose)

With caution:

patients who abuse alcohol, history of liver disease, patients after organ transplantation who are receiving immunosuppressant therapy (due to the increased risk of

rhabdomyolysis and renal failure); concomitant use with dronedarone, ranolazine, fibrates (except gemfibrozil and fenofibrate), amiodarone, “slow” calcium channel blockers

(verapamil, diltiazem, amlodipine), lomitapide (increased risk of myopathy and rhabdomyolysis); Patients with severe chronic renal insufficiency (creatinine clearance less than 30 ml/min);

conditions that may lead to significant renal failure, such as arterial hypotension, acute severe infectious diseases, severe metabolic and endocrine

disorders, water-electrolyte balance disorders, surgical interventions (including dental) or trauma; patients with diabetes; patients with reduced or increased skeletal muscle tone of unclear etiology; epilepsy.

Side effects

Frequency of side effects: very frequently (≥ 1/10), frequently (≥ 1/100, but < 1/10), infrequently (≥ 1/1000, but < 1/100), rarely (≥ 1/10000, but < 1/1000), very rarely (< 1/10000), including individual reports, frequency not established (impossible to estimate based on available data)

Digestive system disorders: Rarely, abdominal pain, constipation, flatulence, dyspepsia, nausea, vomiting, diarrhea, pancreatitis, hepatitis/jaundice; very rarely, fatal and nonfatal liver failure.

Nervous system: rare – asthenic syndrome, headache, dizziness, peripheral neuropathy, paresthesia; very rare – sleep disorders, including insomnia and “nightmares” dreams, memory disorders; frequency is not known – depression.

There have been rare post-registration reports of cognitive impairment (e.g., various memory disorders – forgetfulness, memory impairment, amnesia, confusion) associated with statin use.

These cognitive impairments have been reported with all statins. The reports were generally classified as non-serious, with varying duration to symptom onset (from 1 day to several years) and time to resolution (median 3 weeks).

Symptoms were reversible and resolved after withdrawal of statin therapy.
Allergic and immunopathological reactions: Rarely, hypersensitivity syndrome developed and was manifested by angioneurotic edema, lupus-like syndrome, rheumatic polymyalgia,

dermatomyositis, vasculitis, thrombocytopenia, eosinophilia, increased erythrocyte sedimentation rate (ESR), arthritis, arthralgia, urticaria, photosensitivity, fever, blood “flushes” to the skin, shortness of breath and general weakness.

Skin: rare – skin rash, itching, alopecia.

Musculoskeletal system: rare – myopathy (including myositis), rhabdomyolysis with or without acute renal failure, myalgia, muscle cramps; frequency is not determined – tendinopathy, possibly with tendon rupture.

There have been very rare reports of immune-mediated necrotizing myopathy (autoimmune myopathy) due to statin intake, characterized by proximal

muscle weakness and elevated serum creatine phosphokinase (CPK) activity that persists despite statin treatment withdrawal. Necrotizing myopathy without significant inflammation is observed on muscle biopsy.

Improvement is observed with immunosuppressant therapy.

Laboratory parameters: rarely – increased activity of “hepatic” transaminases, alkaline phosphatase, creatine phosphokinase.

Increase in glycosylated hemoglobin concentration (HbAlc) and fasting serum glucose concentration during administration of statins, including simvastatin, has been reported.

Other: rare – anemia; frequency is not determined – erectile dysfunction, sexual dysfunction, gynecomastia, interstitial lung disease.

Overdose

None of the known few cases of overdose (maximum dose taken 450 mg) have shown specific symptoms.

Treatment: induce vomiting, take activated charcoal. Symptomatic therapy. Liver and renal functions and serum CPK levels should be monitored.

In case of myopathy with rhabdomyolysis and acute renal failure (a rare but severe side effect) the drug should be stopped immediately and the patient should be given a diuretic and sodium bicarbonate (intravenous infusion). Hemodialysis is indicated if necessary.

Rhabdomyolysis may cause hyperkalemia, which may be managed by intravenous calcium chloride or calcium gluconate administration, glucose and insulin infusion, use of potassium ion exchangers or, in severe cases, with hemodialysis.

Pregnancy use

Simvastatin may have adverse effects on the fetus and is contraindicated in pregnant women. There have been several reports of abnormalities in newborns whose mothers have taken Simvastatin.

Women of reproductive age taking Simvastatin should avoid conception. The use of Simvastatin is not recommended in women of childbearing age who do not use contraceptives.

If pregnancy does occur during treatment, Simvastatin should be discontinued and the woman should be warned of the possible risk to the fetus.

There are no data on excretion of Simvastatin with maternal milk.

If Simvastatin must be prescribed while breastfeeding, it should be taken into account that many drugs are excreted with breast milk, and there is a risk of severe reactions, so breastfeeding while taking the drug is not recommended.

Similarities

Vasilip, Simvastatin