Mevacor

Mevacor is a lipid-lowering drug from the statin category. It slows down the activity of HMG-CoA reductase.

Indications Mevacore

It is used for therapy in the following cases:

• primary hypercholesterolemia (hypolipidemia of form IIa and IIb), against which a high level of LDL is observed (if diet therapy in people with an increased risk of developing coronary atherosclerosis has not had the desired effect);
• hypercholesterolemia, as well as combined hypertriglyceridemia;
• atherosclerosis.

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Release form

The release occurs in tablets, 14 pieces inside a blister plate. In a pack - 2 such plates.

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Pharmacodynamics

The lactone-type statin ring is structurally similar to a portion of the HMG-CoA reductase enzyme. Using a competitive antagonism scheme, the statin molecule is synthesized with the end portion of coenzyme A to which the enzyme is attached. The second portion of this molecule slows down the process of transforming hydroxymethylglutarate into the element mevalonate, which is an intermediate component of cholesterol molecule binding.

Slowing down the activity of HMG-CoA reductase causes a series of sequential reaction manifestations, as a result of which a decrease in the intracellular level of cholesterol occurs, as well as a compensatory increase in the activity of LDL endings, according to which cholesterol catabolism of LDL is accelerated.

The hypolipidemic effect of statins develops due to a decrease in the values of total cholesterol due to the elements of LDL cholesterol. The decrease in LDL values depends on the portion size and has exponential rather than linear parameters.

Statins do not affect hepatic or lipoprotein lipase, and in addition, they do not have a significant effect on the catabolism and binding of free fatty acids. Because of this, their effect on TG values is secondary and mediated by the main effects of reducing LDL-C values. The moderate decrease in TG values that occurs during statin therapy is most likely caused by the expression of remnant-type endings (apo E) located on the surface of hepatocytes, which are participants in the processes of IDL catabolism and contain about 30% of TG.

Controlled trials have shown that lovastatin increases HDL-C levels by up to 10%.

In addition to the hypolipidemic effect, statins have a positive effect in the case of endothelial dysfunction (a preclinical symptom of early-stage atherosclerosis), as well as in relation to the walls of blood vessels and the state of atheroma. At the same time, they improve the rheological characteristics of the blood and have an antiproliferative and antioxidant effect.

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Pharmacokinetics

In the gastrointestinal tract, the drug is absorbed incompletely (approximately 30% of the portion) and slowly after oral administration. Taking the drug on an empty stomach reduces absorption by approximately 30%. The level of bioavailability of the drug that has entered the circulatory system is limited due to active extraction during the first liver passage, after which the substance is excreted with bile. Peak values of the active element and its metabolic products in the blood plasma are noted after 2-4 hours after taking a single portion.

The indicators of metabolic products in the blood plasma increase linearly in accordance with the increase in the dose of the drug to 120 mg.

The synthesis of Mevacor and its active decay products with blood plasma protein is more than 95%. The drug passes through the BBB and placenta, and also accumulates in the liver, where it undergoes a hydrolysis process, during which active and inactive metabolic products are formed. Among the main active decay products are 6-hydroxy; and also 6-hydroxymethyl and 6-hydroxymethylene derivatives of b-hydroxy acid.

With daily single administration of the drug, stable plasma indices of its active, and in addition to this, inactive inhibitor substances are noted after 2-3 days of treatment. These values are approximately 1.5 times higher than the index of drug metabolism products when taking a single dose.

Approximately 10% of the substance is excreted in urine, and approximately 83% in feces. The portion of the drug that was excreted in bile, as well as its unabsorbed portion, is excreted in feces. The half-life of lovastatin is 3 hours.

In people with severe renal failure (the level of CC is within 10-30 ml/minute), the indicators of active and inactive products of drug metabolism in the blood plasma after taking a single dose of the drug are approximately twice as high as similar values in the blood plasma in healthy people.

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Dosing and administration

The medicine is taken orally. The initial dose is 10-20 mg, taken once a day – in the evening, with food. If necessary, the dose can be increased, but this is allowed only once per month.

The maximum daily dose is 80 mg, taken in 1 or 2 doses (with breakfast and dinner). If plasma cholesterol levels drop to 140 mg/dl (3.6 mmol/l) or LDL-C drops to 75 mg/dl (1.94 mmol/l), the dose of lovastatin should be reduced.

When combining the drug with immunosuppressants, no more than 20 mg of lovastatin should be taken per day.

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Use Mevacore during pregnancy

Mevacor should not be administered to pregnant or breastfeeding women.

Contraindications

Main contraindications:

• acute liver pathologies;
• increased activity of liver transaminases in the blood serum (of unknown origin);
• suspicion of pregnancy;
• general severe condition of the patient;
• presence of intolerance to lovastatin.

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Side effects Mevacore

The use of the drug can cause various side effects:

• digestive disorders: heartburn. Constipation, nausea, bloating, vomiting and dry mouth are occasionally observed, as well as anorexia, taste disorders and increased activity of liver transaminases in the blood. Hepatitis, liver dysfunction, intrahepatic cholestasis, gastralgia and pancreatitis are observed sporadically;
• lesions affecting the structure of bones and muscles: myopathy with myalgia, as well as myositis or rhabdomyolysis (in case of combination with gemfibrozil, cyclosporine or niacin), as well as arthralgia and an increase in the level of extracardiac fraction of CPK in the blood plasma;
• disorders of the central nervous system and the peripheral nervous system: the appearance of headaches, dizziness, convulsions with paresthesia or sleep problems. Mental disorders are occasionally noted;
• problems with the hematopoietic system: leukopenia or thrombocytopenia, as well as hemolytic anemia;
• lesions affecting the visual organs: clouding of the lens, visual fogging, atrophy affecting the optic nerve, and cataracts;
• signs of allergy: rashes on the epidermis and itching. Tension, angioedema and urticaria are observed sporadically;
• others: decreased potency, and in addition, acute renal failure (caused by rhabdomyolysis), strong heartbeat and pain in the sternum.

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Interactions with other drugs

Combined use with macrolide antibiotics, immunosuppressants (including cyclosporine), gemfibrozil, and also with niacin increases the likelihood of rhabdomyolysis, which then leads to acute renal failure (especially in people with diabetic glomerulosclerosis).

Combination of drugs with derivatives of indandione and coumarin, as well as with anticoagulants, causes increased bleeding and prolongation of PT values.

Taking the medication together with oral contraception can prevent the development of hyperlipidemia caused by the use of hormonal contraception.

It is believed that a decrease in the hypolipidemic effect of lovastatin is observed when combined with thiazide and loop diuretics.

Verapamil with diltiazem, and in addition isradipine, slow down the activity of the CYP3A4 isoenzyme, which is involved in the metabolism of the substance lovastatin. Because of this, when they are combined with Mevacor, the plasma level of lovastatin and the likelihood of myopathy may increase.

There is evidence that when combined with itraconazole, hepatotoxicity and rhabdomyolysis may develop in the acute stage.

A single case of severe hyperkalemia has been described in a patient with diabetes mellitus as a result of taking the drug together with lisinopril.

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Storage conditions

Mevacor should be kept in a dark and dry place at temperatures not exceeding 25°C.

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Shelf life

Mevacor can be used for 3 years from the date of manufacture of the drug.

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Application for children

There is no information regarding the effectiveness and safety of the drug for children.

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Analogues

The analogs of the drug are Amvastan, Lescol and Choletar with Lipantil.

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