Lovastatin is an inhibitor of endogenous cholesterol synthesis in the liver. In the body, lovastatin, anadrol for sale anadrol for sale in the form of inactive lactone, is hydrolysed directly to the corresponding β-hydroxy – therapeutically active form. This active form acts as a competitive inhibitor Z-W-hydroxy-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) – an enzyme that catalyzes the conversion of HMG-CoA to mevalonate – an initial step of cholesterol biosynthesis. Effective in lowering total cholesterol and cholesterol composition of low density lipoprotein (LDL) and very low density lipoprotein (VLDL). Content decreases and decreases apolipoprotein B concentration in plasma triglycerides and moderate increases the concentration of high density lipoprotein (LPVGG). Other effects of lovastatin (improvement of endothelial function, plaque stabilization, anti-inflammatory and anti-thrombogenic effect), some of which are not directly related to the effect of lipid-lowering, anti-atherosclerotic effect of lovastatin contribute pronounced therapeutic effect of the drug is for 2 weeks, and the maximum -through 4-6 weeks after the start of treatment and continued for 4-6 weeks after discontinuation of therapy. Lovastatin efficacy in long-term use (up to 5 years) is not reduced.
In the gastrointestinal tract (GIT) is absorbed slowly and incompletely – about 30% of the dose, fasted absorption reduces by 1/3 compared with the reception together with food. The time to maximum concentration (T Cmax ) – 2-4 hours, the maximum concentration (C max ) – 7.8 ng / ml and 11.9 ng of lovastatin / ml for beta-hydroxy acid, and then the plasma concentration decreases rapidly, amounting to over 24 h 10% of the maximum.
Communication with plasma proteins – 95%. Clearance of lovastatin and its active metabolite by a single appointment for the night is achieved by 2-3 days.therapy and 1.5 times higher than after a single dose. It penetrates through the blood-brain barrier (BBB) and the placental barrier.
Subjected to intensive metabolism in the “first pass” through the liver, is oxidized to a beta-hydroxy acid, its 6-oxyderivatives et al. Metabolites, some of which are pharmacologically active (inhibit HMG-CoA reductase) . The metabolism of the drug involved isozymes CYP3A4, CYP3A5 and CYP3A7. The half-life (T1 / 2) -. 3 hours is derived through the intestines – 83% -10% by the kidneys.
- For lowering elevated serum total cholesterol, LDL cholesterol and triglycerides in the blood serum of patients with primary hypercholesterolemia (Types IIa and IIb according to Fredrickson) including heterozygous familial hypercholesterolemia, polygenic hypercholesterolemia, and mixed hyperlipidemia. The drug is indicated for the lack of effectiveness of diet therapy and other non-drug measures.
- Treatment of coronary atherosclerosis in patients with coronary heart disease (CHD) in order to slow it progressed.Contraindications
- Increased individual sensitivity to lovastatinu or other ingredients;
- liver disease in the active phase or a persistent increase in activity of “liver” transaminases of unknown etiology;
- pregnancy and lactation;
- age of 18 years (effectiveness and safety have been established)
- lactose intolerance, lactase deficiency or glucose-galactose malabsorption.Precautions: liver disease (history), chronic alcoholism, organ transplantation, concomitant immunosuppressive therapy, chronic renal failure (CRF), urgent (emergency) surgical procedures (including dental), while taking gemfibrozil, fenofibrate and other fibrates , nicotinic acid (more than 1 g / d.) (because of the risk of myopathy), cyclosporine, nefazodone, macrolides (erythromycin, clarithromycin), antifungal agents from the group of “Nitrogen” (ketoconazole, itraconazole) and HIV protease inhibitor (ritonavir) .Pregnancy and lactation
The drug is contraindicated during pregnancy and lactation. During treatment with lovastatin, women of childbearing age should use reliable contraception.
It is not known whether lovastatin is excreted in breast milk. Therefore, if the drug during this period is required, breast-feeding should be abolished.
Dosing and Administration
Inside, during a meal. Prior to drug administration and during use, the patient should be assigned to a standard hypocholesterolemic diet. Hyperlipidemia recommended dose of lovastatin 10 to 80 mg once a day. Typically, the initial dose in patients with moderate hypercholesterolemia is 20 mg once a day during the evening meal; in patients with severe hypercholesterolemia (total cholesterol in the blood plasma of 7.8 mmol / L) – 40 mg / day. If necessary to reach target cholesterol values in serum Lovastatin drug dose may be increased to a maximum daily dose of 80 mg per day in single or divided doses (at breakfast and dinner). Changes (selection) the dose should be performed at intervals of not less than 4 weeks. In the case of reducing the total cholesterol anadrol for sale anadrol for sale concentration in blood plasma to 140mg / 100ml (3.6 mmol / L) or LDL – cholesterol to 75 mg / 100 ml (1.94 mmol / L), the dose should be reduced. If a patient receives both cyclosporine, fibrates or nicotinic acid (more than 1 g per day) – the maximum daily dose of the drug lovastatin should not exceed 20 mg / day. Lovastatin dose above 20 mg / day. patients with severe renal failure (creatinine clearance (CC) is less than 30 ml / min., and / or 0.5 ml / sec) should be taken with caution and control. Coronary atherosclerosis Daily dosages are from 20 mg to 80 mg in single or divided 2 reception dosage and duration of admission determined by the doctor.
The drug Lovastatin is usually well tolerated by patients. From the digestive system: often – heartburn, nausea, abdominal pain, constipation or diarrhea, flatulence, dyspepsia; very rarely – dry mouth, taste perversion, biliary cholestasis, hepatitis, gastralgia, cholestatic jaundice, hepatic dysfunction, hepatitis, acute pancreatitis. On the part of the central and peripheral nervous system: often – headache, dizziness; very rarely – peripheral neuropathy, sleep disorders, fatigue, insomnia, paresthesia, mental disorders (including anxiety). From the musculoskeletal system: often – myalgia, muscle cramps; rare – myopathy, myositis, dermatomyositis; very rarely – in patients taking both ciclosporin, gemfibrozil or nicotinic acid increased risk of rhabdomyolysis. From the side of hematopoiesis: hemolytic anemia, leukopenia, thrombocytopenia. From a sight organ: very rarely – “fog” before the eyes, cataract, cataract, optic atrophy Laboratory indicators: a moderate increase in activity of “liver” enzymes: alanine aminotransferase (ALT) and asparaginaminotransferazy (AST) (including a three-fold increase in relation to the upper limit of normal – in 1.5% of cases); rarely -increasing activity of creatine phosphokinase (CK); very rare – increase in alkaline phosphatase and bilirubin. Allergic reactions: very rarely – hypersensitivity syndrome (anaphylaxis, lupus-like syndrome, arthralgia, angioedema, urticaria, erythema multiforme, including Stevens – Johnson), toxic epidermal necrolysis (Lyell’s syndrome), skin rash, itching. Other: very rarely – reduced potency, acute renal failure (due to rhabdomyolysis), chest pain, palpitations, alopecia.
described several cases of accidental admission of unnecessarily large doses of the drug, but the specific symptoms in patients with no observed. Treatment: removal of preparation, general activities: monitoring and maintenance of vital functions, preventing further absorption of the drug (gastric lavage, activated charcoal or laxatives) , you need to monitor liver function and CK activity. There is no specific antidote, hemodialysis is not effective.
The interaction with other drugs
Simultaneous administration of the drug lovastatin and nicotinic acid (more than 1 g / d.), Cyclosporine, macrolide antibiotics (erythromycin, clarithromycin) “azole” antifungals (ketoconazole, itraconazole), HIV protease inhibitors (ritonavir), nefazodone may increase the lovastatin concentration in the blood plasma, which can occur due to rhabdomyolysis and myopathy, renal insufficiency. Grapefruit juice in large quantities (over 1 liter / day.) Increases with max and area under the curve “concentration-time” (the AUC) of lovastatin, and the risk of myopathy. Simultaneous administration of the drug Lovastatin with fibric acid derivatives (gemfibrozil, fenofibrate, etc.) Can also lead to the development of myopathy, although the mechanism in this case is unclear.
Co-administration of the drug lovastatin and warfarin may intensify the effect of the latter on the parameters of blood clotting in connection with what may increase the risk of bleeding. In the case of co-administration of these two drugs is recommended to carry out an appropriate frequency determination of prothrombin time until reaching the stable figures of this indicator. Cholestyramine and colestipol reduce bioavailability (lovastatin may use 2-4 hr. After administration of these drugs, while noting additive effect).
Treatment with lovastatin should be accompanied by an appropriate diet (low cholesterol).
Therapy drug Lovastatin can cause increased activity of “liver” enzymes. This increase is usually small and clinically insignificant. However, it is recommended to control enzyme levels before treatment and during treatment at regular intervals (for one year, then at least one fold at 6 months).
When the ACT activity and / or serum ALT 3 times the upper limit of norm treatment with lovastatin should be discontinued. Drug treatment should be discontinued in the event of a persistent increase of CPK activity. This should be considered in the differential diagnosis of chest pain. Lovastatin therapy drug can lead to myopathy, and as a consequence, to rhabdomyolysis and renal failure. The risk of this disease increases in patients receiving both, one or more of the following drugs: fibrates (gemfibrozil, fenofibrate), cyclosporine, nefazodone, macrolides (erythromycin, clarithromycin), antifungal agents of “azole” group (ketoconazole, itraconazole) and inhibitors HIV proteases (ritonavir). The risk of myopathy is also increased in patients with severe renal impairment.
Patients should promptly inform the doctor in case of unexplained pain in the muscles, especially if accompanied by malaise or fever.
Care should be taken when using Lovastatin drug in patients who consume excessive amounts of alcohol, and patients with a history of liver disease.
in the period of treatment with lovastatin, women of childbearing age should use reliable contraception.
Lovastatin is less effective in patients with rare homozygous familial hypercholesterolemia, possibly because these patients are no functioning LDL receptors. Apparently, these patients will Lovastatin is capable of increasing the activity of “liver” enzymes.
Lovastatin has only a modest effect in reducing triglycerides and not shown in the cases where the primary pathology is hypertriglyceridemia (hyperlipidemia i.e. I, IV and V types according to Fredrickson).
Effects on ability to drive and other complex mechanisms:
There was no any effect on the ability to drive anadrol for sale anadrol for sale a car or work with technical devices.