Fluvastatin, synthetic cholesterol-lowering drug is a competitive inhibitor of the enzyme HMG-CoA reductase responsible for the conversion of HMG-CoA to mevalonate – a precursor of sterols, including cholesterol (Xc). Fluvastatin inhibits cholesterol synthesis in the liver.It is mainly a racemate of the two eritroenantiomerov, one of which has pharmacological activity. When testosterone suspension cycle depression of cholesterol synthesis and a reduction of its content in liver cells compensatory increased formation receptor low-density lipoprotein (LDL), as well as their grip hepatocytes, which reduces the concentration of cholesterol in plasma. Treatment of patients with primary hypercholesterolemia or mixed dyslipidemia Lescol Forte dose 80 mg / day for 24 weeks resulted in a significant decrease in total cholesterol concentration by 23%, it reaches its maximum severity within 4 weeks of starting treatment and is maintained during continuous therapy.patients with primary mixed dyslipidemia lib type classification Fredrickson Leskol the treatment at a dose of 80 mg per day is a decrease in plasma triglyceride concentration by 25% (the initial value of 200 to 400 mg / dl). In patients with ischemic heart disease with concomitant hypercholesterolemia (LDL-C 115 190 mg / dL), the use of fluvastatin 40 mg / day for 2.5 years caused a significant slowdown in the progression of coronary atherosclerosis (according to angiographic studies). The use of fluvastatin in patients with CHD at various concentrations of total cholesterol dostaverno reduces the risk of serious cardiovascular events first (sudden cardiac death, myocardial infarction, need for revascularization, and coronary bypass surgery) for 4 years. This positive effect is particularly pronounced in patients with diabetes mellitus and multiple lesions of the coronary arteries. Therapy Lescol Forte reduces by 31% the risk of myocardial infarction and / or sudden cardiac death. Displaying a decrease in total cholesterol concentrations by an average of 30.5%, LDL-C – 23.6%, TG – by 5.2% and increase Hs- HDL – 5% when using fluvastatin for two years in children and adolescents over 9 years with heterozygous familial hypercholesterolemia if:
- initial concentration of LDL-C> 190 mg / dl (4.9 mmol / L);
- the initial concentration of LDL-C> 160 mg / dL (4.1 mmol / l) and the presence of one or more risk factors (early coronary heart disease with relatives, smoking, high blood pressure, confirmed the level of LDL-HDL cholesterol below 35 mg / dL, diabetes diabetes);
- initial concentration of LDL-C> 160 mg / dl (4.1 mmol / L) TG <600 mg / dl and the defect established (at the DNA level) to the receptors of LDL-C.
Application of fluvastatin in children and adolescents over 9 years of age does not lead to a breach of the growth, development and puberty.
Fluvastatin is not used for the treatment of children and adolescents under the age of 9 years. Presented pharmacodynamic characteristics of fluvastatin, resulting from clinical studies may not be used to evaluate the possible effects of early treatment with statins in children. Pharmacokinetics Absorption When administered in the form of a solution of fluvastatin is absorbed rapidly and completely (98%). After oral tablets Fluvastatin Lescol Forte absorption takes place slowly at 60% compared with conventional dosage forms (capsules) with an average retention time of fluvastatin is increased by approximately 4-hour plasma. Fluvastatin postprandial absorption rate decreased slightly. Distribution bioavailability of the drug is 24%. The apparent volume of distribution of fluvastatin (the V the z / f) is equal to 330 liters.More than 98% of circulating fluvastatin binds to plasma proteins, the degree of coupling is independent of the concentration of fluvastatin in the content nor warfarin plasma salicylic acid and glyburide.Metabolism Fluvastatin is metabolized mostly in the liver. Upon receiving the drug in the blood mainly circulate fluvastatin and pharmacologically inactive metabolite – N-dezizopropil-propionic acid.Hydroxylated metabolites possess pharmacological activity in the systemic circulation but they do not fall. Path biotransformation fluvastatin not associated with cytochrome P450 metabolism fluvastatin therefore practically not altered by drugs affecting cytochrome P450. Fluvastatin inhibited only isoenzyme CYP2C9. Despite the possible competition between fluvastatin and substrates isoenzyme of CYP2C9, such as diclofenac, phenytoin, tolbutamide and warfarin, according to clinical research drug interactions are unlikely. Write mainly through the intestine (93%) and 6% by the kidneys, and the share of unmodified fluvastatin accounts less than 2%. The calculated value of plasma clearance (CL / f) of fluvastatin in humans is 1.8 ± 0.8 L / min. The values of the equilibrium plasma concentrations showed no accumulation of fluvastatin after his appointment at a dose of 80 mg per day. After a single dose of 80 mg Lescol Forte fasting half-life of fluvastatin was 7,0 ± 3.8 hours. When assigning fluvastatin during or after dinner 4 hours after dinner significant differences in AUC value was identified. The concentration of fluvastatin in plasma independent of sex or age of the patient. However, noted the presence of a more pronounced effect on the use of fluvastatin in women and older patients. Fluvastatin has a high degree of first-pass metabolism is output via the biliary tract. There is a possibility of cumulation of the drug in patients with hepatic insufficiency.
Indications Adults (over 18 years)
- Primary hypercholesterolaemia and mixed dyslipidaemia (type IIa and IIb Fredrickson classification) in combination with diet;
- coronary atherosclerosis in patients with coronary heart disease and primary hypercholesterolemia, including slightly pronounced (to slow the progression of the disease).
- secondary prevention of major serious cardiovascular events (sudden cardiac death, myocardial infarction and coronary revascularisation) in patients with coronary heart disease after percutaneous transluminal balloon angioneoplastiki.
Children and adolescents (over 9 years)
- heterozygous familial hypercholesterolemia in combination with diet.
Hypersensitivity to fluvastatin or any inactive ingredients of the drug.
- Active liver disease or persistent increase in concentrations of serum transaminases of unknown etiology.
- Pregnancy, lactation.
Precautions Hepatic function Caution should be exercised in the appointment of patients with a history of liver disease or abuse alcohol. Skeletal muscles Caution must be exercised when administered to patients with a predisposition to rhabdomyolysis, as well as hereditary muscular diseases, muscular toxicity cases when other statins or fibrates in history .
Pregnancy and lactation
Since HMG-CoA reductase inhibitors decrease the synthesis of cholesterol and possibly other biologically active substances – derivatives of cholesterol, in the appointment of these drugs to pregnant women may harm the fetus. Therefore, use of fluvastatin is contraindicated during pregnancy and lactation. Women of childbearing age should use adequate contraception methods. If during treatment with drugs in this pharmacological group pregnancy occurs, treatment should be discontinued. Contraindicated use of fluvastatin during breastfeeding.
Dosage and administration:
Tablets Lescol Forte can be taken once daily without regard to food. Lescol Forte should be swallowed whole, washed down with a glass of water. There were no significant differences in the lipid-lowering effect of fluvastatin in the appointment of a meal or 4 hours after it was observed. Since fluvastatin does not react with substances that are substrates for isoenzyme of CYP3A4, is not expected to interact with grapefruit juice.
There was no reduction of lipid-lowering action of fluvastatin in appointing him during or after 4 hours after the evening meal.
Since the maximum lipid-lowering effect of the drug is developed to the 4 week The first revision of the dose is carried out depending on the achieved effect, at intervals of not less than 4 weeks. The therapeutic effect of Lescol Forte is saved when his long-term use.
Before treatment, the patient Lescol Forte need to be translated into a standard hypolipidemic diet. The diet must be observed during the treatment period.
The initial recommended dose is 80 mg (1 tablet Lescol Forte 80 mg), 1 per day. In mild cases of the disease may be sufficient dose of 20 mg fluvastatin (1 capsule Lescol 20 mg) .Nachalnuyu dose should be individualized, taking into account the source of cholesterol / LDL levels, and the goal of therapy.
For patients with coronary heart disease after surgery angioneoplasticheskoy recommended starting dose is 80 mg per day.
Lescol Forte effective when used as monotherapy. There is evidence for the efficacy and safety of fluvastatin when combined with nicotinic acid, cholestyramine or fibrates. Children and teenagers under 18 years of age. Children and adolescents over 9 years within 6 months prior to initiating therapy Lescol Forte and during the treatment period should follow standard hypolipidemic diet. The recommended starting dose is 80 mg (1 tablet Lescol Forte 80 mg), 1 per day. In mild cases may be sufficient dose of 20 mg fluvastatin (Lescol 1 capsule 20 mg). The initial dose should be adjusted individually according to the baseline LDL-C and treatment purposes. The use of fluvastatin in conjunction with nicotinic acid, kolestiraminom or fibrates in children and adolescents has not been studied. Patients with renal impairment Since fluvastatin is derived largely by the liver and less than 6 % in the body the dose excreted in the urine in patients with impaired renal function, any severity not necessary correction dose.patients with hepatic impairment is contraindicated the use of Lescol Forte with active liver disease or persistent elevations of concentration of serum transaminases of unknown etiology. patients olderEfficacy and tolerability of fluvastatin was demonstrated for patients like 65 years and under this age. In the age group of 65 years and the response to treatment was more pronounced, with no evidence of tolerance to the worst, it has been received. Thus, there is no need to change the dose of Lescol Forte based on age.
The following adverse events are listed by frequency, beginning with the most frequent. The frequency of adverse reactions was evaluated as follows: Emerging “very often” – ≥1 / 10, “often” – ≥1 / 100 ≤1 / 10, “sometimes” – ≥1 / 1000 ≤1 / 100, “rarely” – ≥ 1/10 000 ≤1 / 1000 “very rare” – ≤1 / 10,000, including isolated reports. Within each group, selected by the frequency of occurrence, adverse reactions are distributed in order of their importance.
Among the observed side-effects most frequently observed mild symptoms of gastro-intestinal tract, insomnia and headache. From the hematopoietic system and lymphatic system: very rarely – thrombocytopenia. Psychiatric disorders: often -bessonnitsa. From the nervous system: often – headache; very rarely – paresthesia, dysesthesia, hypoesthesia, possibly related to the underlying disease.From the circulatory system: very rarely – vasculitis. On the part of the gastrointestinal tract: often – indigestion, abdominal pain, nausea; testosterone suspension cycle very rarely – pancreatitis. Liver: very rarely – hepatitis. Skin and subcutaneous tissue: rarely – hypersensitivity reactions such as rash, urticaria; very rarely – other skin reactions (eczema, dermatitis, bullous exanthema), face edema, angioedema. From the musculoskeletal system: rarely – myalgia, muscle weakness, myopathy; very rarely – myositis, rhabdomyolysis, lupus-like reactions. Laboratory findings Increased transaminase concentrations in blood serum to values more than 3 times the upper limit of normal (1-2%). The marked increase in the levels of creatine phosphokinase (CPK) – more than 5 times exceeding the upper limit of normal (0.3-1%). The safety profile of the use of fluvastatin in children and adolescents with geterozigotnoysemeynoy hypercholesterolemia, which was estimated in two clinical studies did not differ from the set for adults. In both clinical trials in children and adolescents have normal processes of growth and sexual development.
In a placebo-controlled studies in 40 patients with hypercholesterolemia treated with Lescol fort at a dose of 320 mg daily for 2 weeks, was well tolerated, If accidental drug overdose shown symptomatic treatment and making all the necessary measures to ensure the maintenance of the vital functions of the body .
Interaction with other medicinal products and other forms of interaction The effect of various drugs on fluvastatin Fibrates and niacin. When concomitant administration of fluvastatin with bezafibrate, gemfibrozil, ciprofibrate or niacin any clinically significant changes in the bioavailability of these drugs were observed. However, since, while the use of other inhibitors of HMG-CoA reductase vysheukazannymi_lekarstvennymi means there was an increase risk of myopathy, apply such combinations should be cautious. Itraconazole and erythromycin. Co-administration of fluvastatin and these potent inhibitors of CYP ZA4 as itraconazole and erythromycin has little effect on the bioavailability of fluvastatin. Since the CYP ZA4 not play any significant role in the metabolism of fluvastatin, it can be expected that other inhibitors of this isoenzyme (ketoconazole, cyclosporin) will have no effect on the bioavailability of fluvastatin. Fluconazole. Assignment fluvastatin healthy volunteers pretreated with fluconazole (an inhibitor of CYP 2C9 ) led to an increase in AUC and fluvastatin Sshah plasma by 84% and 44% respectively. Although it was not received any clinical evidence of change fluvastatin safety profile in patients treated with the prior 4-day treatment with fluconazole should be careful when they are used together. Cyclosporine. In clinical studies in patients with a kidney transplant, receiving a stable maintenance doses of cyclosporin, no It had a clinically significant increase in bioavailability of fluvastatin, at a daily dose assigned to 40 mg. In another study, when assigning Lescol Forte 80 mg kidney transplant patients who received maintenance dose of cyclosporin stable, showed an increase in AUC and C max fluvastatin 2-fold, compared to healthy volunteers. Despite the fact that the increase in AUC and C max of fluvastatin were not clinically significant, caution should be exercised when using this combination. Bile acid sequestrants. Fluvastatin should be administered no earlier than 4 hours after taking cholestyramine to avoid binding the drug. Rifampin. In designation fluvastatin healthy volunteers pretreated with rifampicin was observed decrease fluvastatin bioavailability by approximately 50%. While there is currently no proven change in the activity of fluvastatin when administered to patients receiving long-term treatment with rifampicin (eg for tuberculosis), however, to achieve the desired lipid-lowering effects and may require appropriate dosage adjustment of fluvastatin. Blockers of histamine H 2 receptor antagonists and inhibitors of proton pump. Co-administration of fluvastatin with cimetidine, ranitidine or omeprazole increases bioavailability fluvastatin, which, however, has no clinical significance. Although studies on the interaction of fluvastatin with other drugs of the pharmaceutical groups were not carried out, however, any significant impact of these drugs on the bioavailability of fluvastatin is unlikely. Phenytoin. Effect of phenytoin on the pharmacokinetic parameters of fluvastatin is very small, so to change the dose of fluvastatin is not required. Cordially -sosudistye means. There were no clinically significant pharmacokinetic interactions, while the use of fluvastatin with propranolol, digoxin, losartan or amlodipine, so when using these combinations do not require monitoring of drug concentrations in plasma and correct its dose. The effect of fluvastatin on other drugs Cyclosporin. when concomitant use of fluvastatin 40 mg cyclosporin bioavailability last changes were noted. colchicine. Data on the pharmacokinetic interaction between fluvastatin and colchicine is not. However, when using fluvastatin with colchicine in some cases developed myopathy (muscle pain, muscle weakness and rhabdomyolysis). Phenytoin. Changes in pharmacokinetic parameters of phenytoin while the use of fluvastatin are relatively small and clinically insignificant, so the use of such combinations is enough to carry out conventional monitoring of phenytoin plasma concentrations. Warfarin and other coumarin derivatives. In healthy volunteers at a single dose of fluvastatin and warfarin were observed adverse effect concentration warfarin in plasma and prothrombin time. However, there are very rare reports of bleeding and / or increased prothrombin time have been reported in patients on fluvastatin treatment, while the appointment of warfarin or other coumarin derivatives. Therefore, patients on warfarin therapy, or other coumarin derivatives, it is recommended to monitor the prothrombin time in the event of a cancellation or fluvastatin therapy and in case of changing the dose. Oral hypoglycemic agents. Patients with type 2 diabetes (insulin-dependent) treated with sulfonylureas (glibenclamide, tolbutamide), add to the therapy of fluvastatin does not cause clinically significant changes in blood glucose profile. It has been shown that in 32 patients with non-insulin dependent diabetes mellitus treated with glibenclamide on background simultaneous application fluvastatin 40 mg twice a day for 14 days, there was an increase of mean values Cmax, AUC, and tl / 2 glibenclamide about 50%, 69% and 121%, respectively. Thus, glibenclamide at a dose of 5 mg to 20 mg causes an increase in the mean values C max and AUC for fluvastatin at 44% and 51% respectively. In this study, there were no changes in the levels of glucose, insulin and C-peptide. However, patients taking both fluvastatin and glibenclamide, appropriate monitoring is recommended when increasing the dose to 80 mg of fluvastatin per day.
Cautions Hepatic function in all the patients it is recommended to evaluate liver function before treatment, 12 weeks after starting treatment or increasing dose, and periodically during treatment. If the aspartate aminotransferase activity (ACT) or alanine aminotransferase (ALT) 3 times the upper limit of normal and steadfastly remained at this level, treatment should be discontinued. In very rare cases hepatitis was detected, which may have been associated with taking the drug, and heal after treatment discontinuation. Skeletal muscles When using fluvastatin described rare cases of myopathy, and there are isolated reports of the development of myositis and rhabdomyolysis. When patients with complaints of unexplained diffuse myalgias, muscle tenderness or weakness, and / or detection by testosterone suspension cycle higher levels of creatine phosphokinase (CPK) should be suspected myopathy, myositis or rhabdomyolysis. Patients should be advised to promptly report muscle pain of unknown etiology, pain, or muscle weakness, particularly if accompanied by malaise or fever. Concentration measurement of creatine phosphokinase (CPK) There is currently no evidence of mandatory controls need the concentration of CK or other muscle enzyme in the blood plasma at the absence of the above symptoms. Do not carry out the measurement of CK after intense exercise, as well as any other factors that increase the concentration of CK. Before treatment, it is recommended to define the concentration of CK in the following cases:
- kidney failure
- Hereditary muscle disease (own or family history)
- Manifestations of muscular toxicity with a statin or fibrate in anamnesis
- alcohol abuse
- In elderly patients (over 70 years) should evaluate the need to determine the concentration of CK in the presence of other factors predisposing to rhabdomyolysis.
In these cases, you should weigh the expected benefits of therapy and the risk of adverse events and closely monitor the patient. In marked increase in CK 5 times or more than the upper limit of normal (ULN), there should be re-measure every 5-7 days to confirm the result. When persistent marked increase in the concentration of CK (> 5VGN) treatment should not be initiated.
In the treatment of fluvastatin when a muscle symptoms (pain, weakness, convulsions), determine the concentration of CK. Treatment should be discontinued in patients with severe increase in the concentration of CK (> 5VGN). When strongly pronounced muscular symptoms, causing constant discomfort, even if the increase in the concentration of CK <5VGN should consider discontinuing therapy.
Upon termination of muscle pain, weakness, seizures, and normalization of concentrations of CK, resumption of fluvastatin or any other statin encouraged not to start with the lowest dose and under close supervision. It was noted an increased risk of myopathy with concomitant use of other inhibitors of HMG-CoA reductase inhibitors and such drugs as immunosuppressants (such as cyclosporin), fibrates, nicotinic acid or erythromycin. However, in clinical trials when using fluvastatin in combination with nicotinic acid, fibrates or myopathy cyclosporin cases were not observed. There are some post-marketing reports of myopathy with the concomitant use of fluvastatin with cyclosporin or colchicine.
Patients receiving such concomitant therapy, fluvastatin should be used with caution. The use of fluvastatin in children and adolescents younger than 18 years efficacy and safety of fluvastatin in a period exceeding 2 years, in children and adolescents under 18 years have not been established. It has been studied the use of fluvastatin in children and adolescents over 9 years only with heterozygous familial hypercholesterolaemia. Homozygous familial hypercholesterolemia is currently no data on the use of fluvastatin in patients with a rare disease homozygous familial hypercholesterolemia. ambroxol clenbuterol is an international product.
long term effects of anabolic steroids mike o’hearn natural anabolic steroid pill