hypercholesterolemia. Treatment of primary hypercholesterolaemia or mixed dyslipidaemia as a supplement to diet therapy when the response to diet or other non-pharmacological treatments (physical exercise, weight loss) is insufficient. Treatment of homozygous familial hypercholesterolaemia, as a supplement to diet therapy and other treatments to lower lipid levels (eg LDL apheresis) or when other treatments are not indicated.Prevention of events from the cardiovascular system. Decrease of morbidity and mortality due to cardiovascular diseases in patients with overt atherosclerosis or diabetes, both normal and elevated cholesterol, as a complement to the procedure aimed at correcting other risk factors and supplementing other therapies to prevent heart disease.
Composition:
1 tabl powl. contains 10 mg, 20 mg or 40 mg simvastatin. The preparation contains lactose.
Action:
The active metabolite of Simvastatin (beta-hydroxy acid) is an inhibitor of 3-hydroxy-3-methylglutarylcoenzyme A reductase (HMG-CoA). This enzyme catalyses the conversion of HMG-CoA to mevalonate, i.e. the early stage of cholesterol biosynthesis. Simvastatin lowers both normal and elevated LDL cholesterol. The mechanism of LDL cholesterol lowering by simvastatin may be the result of both lowering VLDL cholesterol and LDL receptor induction, leading to reduced production and increased catabolism of LDL cholesterol. There is also a significant reduction in apolipoprotein B levels. In addition, simvastatin moderately increases HDL cholesterol and decreases serum triglycerides. After oral administration, no more than 5% of the dose gets into the systemic circulation as a beta-hydroxy acid. The maximum concentration of active inhibitors in the plasma occurs within approx. 1-2 h after administration. The drug and its metabolites bind to plasma proteins in over 95%. Simvastatin is a substrate for CYP3A4, the major metabolites are: beta-hydroxy acid and 4 other active metabolites. 13% of the dose is excreted in the urine, 60% in the faeces.
Contraindications:
Hypersensitivity to simvastatin or to any of the excipients. Active liver disease or persistent, unexplained increase in serum transaminases. Pregnancy and lactation. Concomitant administration of potent CYP3A4 inhibitors (eg Itraconazole, ketoconazole, HIV protease inhibitors, Erythromycin, Clarithromycin, telithromycin and nefazodone).
Precautions:
Carefully use in patients with predisposing factors for rhabdomyolysis: in elderly patients (over 70 years old), with renal dysfunction, with decompensated hypothyroidism, with individual or family history of inherited muscular disorders, with muscle complaints appearing in the past associated with the use of statins or fibrates in a history and in patients who abuse alcohol. In these groups of patients, CK activity should be measured before starting treatment - if the CK activity is higher than 5 times the upper limit of normal, do not start treatment. In these patient groups, the expected benefits of the treatment and the associated risks should be considered, clinical monitoring of the patient being recommended. Drug administration must be discontinued if the creatine kinase activity increases (more than 5 times the upper limit of normal); discontinuation of treatment should be considered if the muscle symptoms are serious even when the CK activity does not exceed 5 times the upper limit of normal. If you suspect myopathy for any other reason, the medicine should be discontinued. If the muscle symptoms go away and the CK values return to normal, re-administration of the statin at the lowest effective dose may be considered with close monitoring of the patient's state of health. Treatment should be discontinued a few days before the planned surgery or in the case of other serious diseases or conditions requiring surgical intervention.Special care should be taken in patients who have elevated serum transaminases. The drug should be discontinued if there is a tendency to increase transaminase levels, especially when it reaches 3 times the upper limit of normal and will persist. The drug should be used with caution in patients who consume significant amounts of alcohol. Due to the lack of data on safety and efficacy, it is not recommended for use in children. The product contains lactose - should not be used in patients with rare hereditary galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose.
Pregnancy and lactation:
The preparation is contraindicated during pregnancy and breastfeeding and in women planning pregnancy.
Side effects:
Rare: anemia, headache, paresthesia, dizziness, peripheral neuropathy, constipation, abdominal pain, bloating, nausea, indigestion, diarrhea, vomiting, pancreatitis, hepatitis and / or jaundice, rash, pruritus, alopecia, myopathy, rhabdomyolysis , muscle pain, muscle cramps, weakness, increase in plasma aminotransferases (ALAT, AST, GGT). In rare cases, hypersensitivity syndrome has been reported, including some of the following conditions: angioneurotic edema, lupus-like syndrome, rheumatic polymyalgia, dermatomyositis, vasculitis, thrombocytopenia, eosinophilia, OB increase, arthritis and arthralgia, urticaria, photosensitivity, fever , redness of the skin, shortness of breath and unwellness.
Dosage:
Orally. Adults.hypercholesterolemia. The patient should use a standard low-cholesterol diet, which should be continued during treatment with the preparation. The initial dose is usually 10-20 mg a day, administered in a single dose in the evening. In patients requiring a significant reduction in LDL-C (above 45%), the starting dose may be 20-40 mg per day administered in a single dose in the evening. Changes in the recommended dosage, if necessary, should be made at intervals of not less than 4 weeks.Homozygous familial hypercholesterolaemiaThe recommended dose is 40 mg / day given in the evening or 80 mg / day in 3 divided doses: 20 mg, 20 mg and 40 mg in the evening. The preparation should be used in these patients together with other methods of treatment aimed at lowering blood lipids (eg LDL apheresis) or if another treatment is not possible.Prevention of events from the cardiovascular system: the usual dose for patients with a high risk of ischemic heart disease, with or without hyperlipidemia is 20-40 mg per day administered as a single dose in the evening. Drug therapy can be undertaken simultaneously with the implementation of diet and exercise. Dose changes, if necessary, should be made at intervals of not less than 4 weeks.Combination therapy: the preparation should be administered more than 2 h before administration of bile acid sequestrants or more than 4 h after administration of these drugs. In patients receiving simultaneously simvastatin and cyclosporin, gemfibrozil, other fibrates (except fenofibrate) or niacin in lipid-lowering doses (≥1 g per day), the simvastatin dose should not exceed 10 mg per day. In patients receiving simvastatin and Amiodarone or Verapamil concomitantly, the simvastatin dose should not exceed 20 mg daily. In patients receiving concomitant simvastatin and diltiazem, the dose of simvastatin should not exceed 40 mg daily. In patients with severe renal impairment (creatinine clearance less than 30 ml / min), simvastatin should be carefully considered at a daily dose of more than 10 mg, and if necessary, very cautiously start treatment. No dose adjustment is required in patients with moderate renal insufficiency and in elderly patients.