Lovastatin - instructions for use, dose, side effects, contraindications

Inhibition of 3-hydroxy-methyl-glutaryl-coenzyme A reductase (HMG-CoA reductase) in hepatocytes, blocking the conversion of HMG-CoA into mevalonic acid, slowing down cholesterol synthesis, increasing the number of receptors for low-density lipoprotein on the hepatocyte membrane and increasing the catabolism of lipoprotein cholesterol. low density.

Pharmacokinetics:

Prodrug. Absorption - 30% (increases with admission with food). The connection with plasma proteins is more than 95%. Biotransformation in the liver (CYP3A3, CYP3A4) with the formation of active beta-hydroxymetabolite. The half-life is 3 hours. Elimination with feces (83%) and kidneys (10%).

Indications:

Hypercholesterolemia: primary with high content low density lipoprotein (types IIa and IIb) in the absence of the effect of diet therapy, combined with hypertriglyceridemia (hyperlipoproteinemia type IIb); atherosclerosis.

ICD-10

IV.E70-E90.E78.2 Mixed hyperlipidemia

Contraindications:

Hypersensitivity.

Hepatic insufficiency, acute liver disease, increased activity of transaminases of unclear etiology.

Pregnancy, breast-feeding.

Carefully:

Diseases of the liver (in the anamnesis), chronic alcoholism, organ transplantation, concomitant immunosuppressive therapy, chronic renal failure, urgent (urgent) surgical manipulations (including dental), while taking with gemfibrozil, fenofibrate and other fibrates, nicotinic acid (more than 1 g per day) (due to the risk of developing myopathy), cyclosporine, nefazodone, macrolides (erythromycin, clarithromycin), antifungal agents from the group of "azoles" (ketoconazole, intraconazole) and HIV protease inhibitors (ritonavir).

Pregnancy and lactation:

Lovastatin is contraindicated in pregnancy and lactation (breastfeeding).

FDA recommendation category X.

Dosing and Administration:

Is taken internally. The initial dose is 10-20 mg once a day in the evening during a meal. 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).If the concentration in the plasma of cholesterol is reduced to 140 mg / dl (3.6 mmol / l) or Low-density lipoprotein cholesterol up to 75 mg / dL (1.94 mmol / L) 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 effects:

Myalgia, myositis, acute necrosis of skeletal muscles; possible the development of acute renal failure.

Flatulence, increased activity of transaminases 2 times or more, constipation, diarrhea, heartburn, stomach pain, nausea.

Dizziness, headache.

Impotence, sleep disturbance, skin rash.

Overdose:

There have been several cases of accidental ingestion of excessively large doses of the drug, but no specific symptoms have been observed in patients.

Treatment: withdrawal of the drug, general measures: control and maintenance of vital functions, prevention of further absorption of the drug (gastric lavage, intake of activated carbon or laxatives), it is necessary to monitor liver function and the activity of creatine phosphokinase. There is no specific antidote, hemodialysis is not effective.

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 the intake of 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 severe hyperkalemia in patients with diabetes, while the use of lisinopril.

Special instructions:

Lipid-lowering therapy in patients with chronic renal failure slows the progression of the disease, maintains glomerular filtration rate and proteinuria development. Lovastatin (20-40 mg daily) is comparable in effectiveness with pravastatin (20mg daily), simvastatin yield (10-20 mg per day) and surpasses fluvastatin by the degree of decrease in concentration low density lipoprotein.

Instructions

Lovastatin (Lovastatinum)