Zocor pills 20mg №28

Mechanism of action

The lipid-lowering drug obtained synthetically from the fermentation product Aspergillus terreus.
In the body, Simvastatin (the active ingredient of the drug Zokor), which is an inactive lactone, undergoes hydrolysis to form the corresponding hydroxy acid derivative. The latter is a major metabolite that has an inhibitory effect on 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) - reductase, an enzyme that catalyzes the initial and cholesterol biosynthesis stage. As a result, as shown in clinical studies, Zocor lowers total plasma cholesterol, low density lipoprotein (LDL) and very low density lipoprotein (VLDL). Zocor causes a decrease in plasma triglycerides, as well as a moderate increase in high-density lipoprotein (HDL) and, thus, reduces the ratio of LDL / HDL and total cholesterol / HDL.
Simvastatin, an active metabolite, is a specific inhibitor of HMG-CoA reductase, an enzyme that catalyzes the formation of mevalonate from HMG-CoA. Since the conversion of HMG-CoA to mevalonat is an early stage of cholesterol biosynthesis, it is believed that the use of Zocor should not cause the accumulation of potentially toxic sterols in the body. In addition, HMG-CoA is easily metabolized to acetyl-Co-A, which is involved in many processes of biosynthesis in the body.
Studies have been conducted therapeutic effect of Zocor on primary hypercholesterolemia, in which the appointment of a diet was insufficient. Zocor is highly effective in reducing total cholesterol and LDL in cases of heterozygous familial and non-familial forms of hypercholesterolemia, as well as in mixed hyperlipidemia, when elevated cholesterol is a risk factor. A noticeable effect was achieved within 2 weeks, the maximum therapeutic effect - within 4-6 weeks after the start of treatment. The effect persisted with continued treatment. Upon termination of therapy with Zocor, the total cholesterol content returned to the initial level before the start of treatment.
In a study of the effect of simvastatin on survival (4S), the effect of Zocor therapy on total mortality (median patient participation time 5.4 years) was evaluated in 4444 patients with coronary artery disease with baseline total cholesterol 212-309 mg / dL (5.5-8.0 mmol / l) In this multicenter, randomized, double-blind, placebo-controlled study Zocor reduced the risk of total mortality by 30%, death from coronary heart disease - by 42%, the incidence of myocardial infarction, confirmed in hospital conditions - by 37%. Moreover, Zocor reduced by 37% the risk of the need for surgery to restore coronary blood flow.
A multicenter, placebo-controlled study (Heart Protection Study / HPS) was conducted in the UK for 5.5 years. The study involved 20,536 patients with coronary artery disease or the risk of its development and the level of total cholesterol from 3.5 mmol / l and above. According to the results of the study, it was found that the use of Zocor reduced the risk of developing heart attack, stroke and reduced the frequency of revascularization operations by 1/3 (after admitting non-compliance with the regimen) while maintaining the safety of using the drug. The study also found that the effectiveness of Zocor did not depend on the initial cholesterol level, the age and sex of the patients, and on the simultaneous treatment of another therapy.

Suction
After oral administration, simvastatin is absorbed from the gastrointestinal tract and enters the systemic circulation.
Distribution
Plasma protein binding is 95%.
In experimental animal studies, it was shown that after oral administration, simvastatin accumulates with high selectivity in the liver, where its concentration is significantly higher than in other tissues.
Metabolism
Simvastatin is exposed to the "first pass" effect through the liver.
The concentration of the active metabolite of simvastatin in the human systemic circulation is less than 5% of the ingested dose.
Removal
Simvastatin is excreted in the bile.

Indications and usage

Coronary heart disease; the drug is indicated to patients:
- to reduce total mortality;
- To reduce the risk of coronary mortality and the prevention of myocardial infarction;
- To reduce the risk of stroke and transient disorders of cerebral circulation;
- to reduce the likelihood of undergoing surgery to restore coronary blood flow (coronary artery bypass surgery and percutaneous transluminal coronary angioplasty);
- To slow the progression of coronary atherosclerosis.
Hypercholesterolemia:
- reduction of elevated levels of total cholesterol and cholesterol / LDL in patients with primary hypercholesterolemia, when the use of diet therapy and other non-pharmacological measures did not bring an adequate effect. Zocor increases HDL and thus reduces the ratio of LDL / HDL and total cholesterol / HDL;
- reduction of elevated cholesterol levels in patients with combined hypercholesterolemia and hypertriglyceridemia, when hypercholesterolemia is a risk factor.

Typically, the initial dose is 10 mg 1 time per day in the evening.
At mild to moderate hypercholesterolemia The initial dose is 5 mg / day.
If you need to use higher doses, the dose should be increased, observing 4-week intervals. The maximum daily dose is 80 mg.
If the LDL level drops below 75 mg / dL (1.94 mmol / L) or the total plasma cholesterol level drops below 140 mg / dL (3.6 mmol / L), reduce the dose of Zocor.
At Ischemic heart disease Zocor is prescribed in an initial dose of 20 mg 1 time per day in the evening. Correction of the dosage regimen, if necessary, should be carried out in the same way as with hypercholesterolemia.
In patients receiving cyclosporine, fibrates, niacin, together with Zocor, the maximum recommended dose is 10 mg / day.
Since Zocor is excreted by the kidneys in small quantities, there is no need to change the dose in patients with moderately severe renal dysfunction. Have patients with severe renal impairment (creatinine clearance less than 30 ml / min) should carefully evaluate the feasibility of prescribing the drug in a dose exceeding 10 mg / day. If such a dose is deemed necessary, it should be administered with caution.

Adverse reactions

During the studies conducted on average for 5.4 years, the safety and tolerability of the drug in the groups of patients who received Zocor (n = 2221) at 20-40 mg / day and placebo (n = 2223) were comparable.
Gastrointestinal: abdominal pain, constipation, flatulence (1% or more); additionally reported cases of nausea, diarrhea, dyspepsia, pancreatitis, vomiting, hepatitis, jaundice; perhaps a pronounced and sustained increase in transaminase activity (more than 3 times higher than the upper limit of normal), as well as alkaline phosphatase and GGT. Deviations in functional liver function tests are usually mild and transient.
Nervous system: headache (0.5-0.9%), dizziness, muscle cramps, paresthesias, peripheral neuropathy.
Allergic reactions: rarely - angioedema, lupus-like syndrome, rheumatic polymyalgia, vasculitis, thrombocytopenia, eosinophilia, increased ESR, arthritis, urticaria, photosensitization, fever, skin flushing, shortness of breath.
Dermatologic: skin rash, itching, alopecia.
Other: asthenia (0.5-0.9%), myalgia, anemia, rhabdomyolysis, increased CK; in rare cases, myopathy.
Zocor is generally well tolerated; there were mainly mild and transient side effects. Less than 2% of patients dropped out of controlled clinical studies due to the development of side effects.

Contraindications

- liver disease (in active phase);
- persistent increase in transaminase activity of unknown etiology;
- pregnancy;
- lactation (breastfeeding);
- Hypersensitivity to the drug.

Pregnancy and breastfeeding

Cancellation of hypolipidemic drugs during pregnancy should not have a significant impact on the results of long-term treatment of primary hypercholesterolemia. In addition, cholesterol and other products of its biosynthesis play a significant role in the development of the fetus, including the synthesis of steroids and cell membranes. Due to the fact that HMG-CoA reductase inhibitors, such as Zocor, inhibit the synthesis of cholesterol and, possibly, other products of its biosynthesis, the drug may have an adverse effect on the fetus when prescribing it to pregnant women.
There are several reports of congenital anomalies in newborns whose mothers took HMG-CoA reductase inhibitors during pregnancy.
Data on the allocation of simvastatin or its metabolites in breast milk are not available.If necessary, the appointment of Zocor woman during lactation should take into account that many drugs are excreted in breast milk, and there is a risk of serious adverse reactions, so breastfeeding is not recommended.
Women of childbearing agetaking Zocor should avoid conception. If pregnancy occurs during treatment with Zocor, the drug should be discontinued, and the woman herself should be warned of the possible danger to the fetus.

Before and during the entire course of Zokor's therapy, the patient must be on a cholesterol diet.
Zocor should be prescribed with caution to patients abusing alcohol and / or having a history of liver disease.
During Zokor's therapy, a transient moderate (less than 3 times) increase in transaminase activity is possible, which is asymptomatic and does not require discontinuation of the drug.
The pronounced and sustained increase in liver transaminase activity (more than 3 times) observed during Zocor's intake period, when treatment was discontinued, usually returned to the initial level. Increased transaminase levels were not associated with jaundice or other clinical symptoms. Some of the patients who showed an increase in transaminase activity, before starting treatment with Zocor, had abnormalities in the results of functional liver tests and / or abused alcohol.
The presence of myopathy should be suspected in any patient with diffuse myalgia, increased muscle sensitivity and / or a pronounced increase in the activity of CPK (10 times the upper limit of the norm). Patients should be informed about the need to inform the doctor about the manifestation of muscle pain, weakness or hypersensitivity of the muscles. If there is a significant increase in the level of CPK, or myopathy is diagnosed or suspected, Zokor's treatment should be stopped.
It is known that the risk of myopathy in the treatment of HMG-CoA reductase inhibitors increases with the simultaneous appointment of immunosuppressive therapy, including cyclosporins, as well as with concomitant treatment with fibric acid derivatives or hypolipidemic nicotinic acid doses.There are isolated reports of the development of severe rhabdomyolysis with secondary acute renal failure . Thus, it is necessary to pay special attention to the risks and benefits of co-administration of simvastatin and immunosuppressive drugs, simvastatin and fibrates, simvastatin and lipid-lowering doses of nicotinic acid.
HMG-CoA reductase inhibitors and antifungal agents derived from azole suppress the formation of cholesterol at various stages of its biosynthesis. If necessary, the combined use of cyclosporine, antifungal drugs for systemic use and Zocor should be discontinued for this period therapy with simvastatin. With simultaneous use of Zocor and antifungal drugs azole derivatives should carefully monitor the condition of patients (may develop weakness, increase in CPK).
Treatment with HMG-CoA reductase inhibitors should be interrupted or discontinued in any patient with an acute, severe condition or suspected myopathy or having another risk factor that predisposes to the development of renal failure due to rhabdomyolysis.
The data of modern long-term clinical trials do not contain information on the adverse effects of simvastatin on the human lens of the eye.
In patients taking coumarin anticoagulants, the prothrombin time should be determined before the start of therapy, and also often enough during the initial period of treatment with Zocor to exclude significant changes in this indicator. As soon as a stable level of prothrombin time is reached, its further determination should be carried out at intervals recommended for monitoring patients receiving anticoagulant therapy. The same procedure should be repeated when changing the dose of simvastatin. In patients who did not take anticoagulants, simvastatin therapy was not associated with the occurrence of bleeding or changes in prothrombin time.
In patients over 65 years of age who received Zocor during controlled clinical trials, the effectiveness of the drug was the same as in the population as a whole, and no significant increase in the incidence of clinical or laboratory side effects was observed.
In patients with homozygous familial hypercholesterolemia, in whom there is a complete lack of LDL receptors, treatment with Zocor, as a rule, does not give the desired clinical result.
Zocor has a moderate effect on reducing triglyceride levels and is not indicated in cases where hypertriglyceridemia is of paramount importance (for example, in types I, IV and V of hyperlipidemia).
Zocor is effective both in monotherapy and in combination with bile acid sequestrants.
Control of laboratory parameters
Before treatment, all patients are recommended to conduct a study of liver function, which should be periodically (for example, semi-annually) repeated during 1 year of treatment or within 1 year after the last dose increase. Patients who have a daily dose of 80 mg should be tested 1 time in 3 months. Particular attention should be paid to patients with increased transaminase activity. These patients need to be tested in the near future and subsequently carried out more frequently. In cases where the level of transaminases increases, especially when exceeding 3 times the upper limit of normal, and is stable, the drug should be discontinued.
Use in pediatrics
Safety and efficacy of the drug in pediatric practice has not been established. Do not recommend prescribing the drug to children.

Several cases of overdose have been reported; none of the patients showed any specific symptoms, no effects were observed. The maximum dose taken is 450 mg.
Treatment: conduct symptomatic therapy.

With simultaneous use with indirect anticoagulants Zocor moderately potentiates the action of the latter.
With the simultaneous use of Zocor with cytostatics, itraconazole, fibrates, high doses of nicotinic acid increases the risk of myopathy.

The drug should be stored at a temperature not exceeding 30 ° C; avoid temporary exposure to temperatures above 50 ° C.
Pharmacy sales terms
The drug is available on prescription.