Description of the active substance:
This information is a reference and it is not enough that the drug has been prescribed by a doctor ..
PHARMACHOLOGIC EFFECT
A hypolipidemic agent from the group of statins, an inhibitor of HMG-CoA reductase. It is a prodrug, since it has in its structure a closed lactone ring, which after hydrolysis into the body is hydrolyzed.
The lactone ring of statins is similar in structure to the portion of the HMG-CoA reductase enzyme. According to the principle of competitive antagonism, the statin molecule binds to that part of the coenzyme A receptor where this enzyme is attached. Another part of the statin molecule inhibits the conversion of hydroxymethylglutarate to mevalonate, an intermediate in the synthesis of the cholesterol molecule. Inhibition of the activity of HMG-CoA reductase results in a series of consecutive reactions that result in a decrease in intracellular cholesterol and a compensatory increase in LDL receptor activity and, accordingly, acceleration of LDL cholesterol catabolism (Xc).
The hypolipidemic effect of statins is associated with a decrease in the level of total cholesterol due to Xc-LDL. The decrease in LDL is dose-dependent and has a non-linear, but an exponential nature.
Statins do not affect the activity of lipoprotein and hepatic lipases, they do not have a significant effect on the synthesis and catabolism of free fatty acids, so their effect on the level of TG is secondary and mediated through their main effects on lowering the level of LDL-C. The moderate decrease in TG levels in statin therapy appears to be due to the expression of the receptor (apo E) receptors on the surface of hepatocytes participating in the catabolism of the disease, which includes approximately 30% TG.
According to controlled studies, lovastatin increases HDL-C level to 10%.
In addition to hypolipidemic action, statins have a positive effect on endothelial dysfunction (preclinical signs of early atherosclerosis), on the vascular wall, the state of atheroma, improve the rheological properties of blood, have antioxidant, antiproliferative properties.
PHARMACOKINETICS
When administered orally, lovastatin is slowly and not completely (about 30% of the dose taken) absorbed from the digestive tract. Admission on an empty stomach reduces absorption by 1/3. C max is reached within 2-4 hours, then the level in the plasma rapidly decreases, making after 24 hours 10% of the maximum. Binding to plasma proteins - 95%. C ss lovastatin and its active metabolites with a single appointment for the night is achieved on the 2-3 day of therapy and 1.5 times higher than after a single dose.
Lovastatin penetrates the GEB and the placental barrier. It is subjected to intensive metabolism during the "first passage" through the liver, oxidized to beta-hydroxy acid, its 6-hydroxy derivative and other metabolites, some of which are pharmacologically active (blocking 3-hydroxy-3-methylglutaryl coenzyme A-reductase). T 1/2- 3 hours. Through the intestine 83% are excreted, 10% - by the kidneys.
INDICATIONS
Primary hypercholesterolemia (hypoglyoproteinemia IIa and IIb types) with a high LDL (if diet therapy is ineffective in patients at increased risk of coronary atherosclerosis), combined hypercholesterolemia and hypertriglyceridemia, atherosclerosis.
DOSING MODE
Is taken internally. The initial dose is 10-20 mg 1 time / day in the evening with meals. If necessary, increase the dose 1 time in 4 weeks.
The maximum daily dose is 80 mg in 1 or 2 doses (during breakfast and dinner). In case of a decrease in the plasma concentration of Xc to 140 mg / dL (3.6 mmol / L) or Xc-LDL to 75 mg / dL (1.94 mmol / L), the dose of lovastatin should be reduced.
With simultaneous use with drugs that suppress immunity, the daily dose of lovastatin should not exceed 20 mg.
SIDE EFFECT
From the side of the digestive system: heartburn; rarely - nausea, diarrhea, constipation, flatulence, dry mouth, taste disorders, anorexia, increased activity of hepatic transaminases in the blood, in isolated cases - cholestatic jaundice, hepatitis, pancreatitis, gastralgia, impaired liver function.
From the musculoskeletal system: myalgia, myopathy, myositis, rhabdomyolysis (with simultaneous application of cyclosporine, gemfibrozil or nicotinic acid), arthralgia, an increase in the content of the extracardiac fraction of CK in the blood plasma.
From the side of the central nervous system and peripheral nervous system: dizziness, headache, sleep disorders, convulsions, paresthesia; in isolated cases - mental disorders.
From the hemopoietic system: hemolytic anemia, leukopenia, thrombocytopenia.
From the side of the organ of vision: blurring of vision, clouding of the lens, cataracts, atrophy of the optic nerve.
Allergic reactions: skin rash, itching; in isolated cases - hives, Quincke's edema, toxic epidermal necrolysis.
Other: decreased potency; acute renal failure (caused by rhabdomyolysis), chest pain, palpitations.
CONTRAINDICATIONS
Acute liver disease, increased activity of hepatic transaminases in the serum of unclear etiology, pregnancy (or its probability), lactation (breastfeeding), severe general condition of the patient, hypersensitivity to lovastatin.
PREGNANCY AND LACTATION
Lovastatin is contraindicated in pregnancy and lactation (breastfeeding).
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated in acute liver disease, increased activity of hepatic transaminases in the serum of unclear etiology. Use with caution in patients with liver disease in history.
SPECIAL INSTRUCTIONS
Use with caution in patients with liver disease in history, as well as in chronic alcoholism.
Lovastatin should be discontinued in the event of a persistent increase in blood levels of hepatic transaminases and / or CK, as well as in the general severe condition of the patient due to some disease.
DRUG INTERACTION
When combined with antibiotics, the group of macrolides, gemfibrozil, immunosuppressants (including cyclosporine), nicotinic acid raises the risk of rhabdomyolysis with the subsequent development of acute renal failure (especially in patients with diabetic nephropathy).
With simultaneous use with anticoagulants, coumarin derivatives and indanedione, there is an increase in bleeding and an increase in prothrombin time.
When used simultaneously with oral contraceptives, lovastatin can prevent hyperlipidemia caused by taking hormonal contraceptives.
It is believed that it is possible to reduce the hypolipidemic action of lovastatin with simultaneous application of "loop" and thiazide diuretics.
Diltiazem, verapamil, isradipine inhibit the isoenzyme CYP3A4, which is involved in the metabolism of lovastatin, therefore, simultaneous use may increase the concentration of lovastatin in the blood plasma and increase the risk of myopathy.
There are reports of the development of acute rhabdomyolysis and hepatotoxicity with concomitant use with itraconazole.
A case of the development of severe hyperkalemia in a patient with diabetes mellitus is described with the simultaneous use of lisinopril.
