HOLETAR

Active material: Lovastatin
When ATH: C10AA02
CCF: Lipid-lowering drugs
When CSF: 01.12.11.03
Manufacturer: KRKA d.d. (Slovenia)

Pharmaceutical form, composition and packaging

Excipients: lactose monohydrate, pre-gelatinized starch, ʙutilgidroksianizol (BHA), dye Color Patient Blue V (E131), corn starch, microcrystalline cellulose, magnesium stearate.

10 PC. – blisters (2) – packs cardboard.
10 PC. – blisters (3) – packs cardboard.

Excipients: lactose monohydrate, pre-gelatinized starch, ʙutilgidroksianizol (BHA), dye Quinoline Yellow (E104), coloring matter Patient Blue V (E131), corn starch, microcrystalline cellulose, magnesium stearate.

10 PC. – blisters (2) – packs cardboard.
10 PC. – blisters (3) – packs cardboard.

DESCRIPTION OF ACTIVE SUBSTANCES

Pharmacological action

Lipid-lowering agents of the statin, HMG-CoA reductase. It is a prodrug, because it has a closed ring laktonovoe, after intake of the hydrolyses.

Laktonovoe ring of Statins in its structure is similar to the part of the enzyme HMG-CoA reductase inhibitors. On the principle of competitive antagonism statina molecule binds with the receptor of Coenzyme a, where the enzyme is attached. Another part of the statin molecule inhibits the process of converting to mevalonate gidroksimetilglutarata, intermediate in the synthesis of cholesterol molecules. Inhibition of HMG-CoA reductase leads to a series of successive reactions, resulting in reduced intracellular cholesterol and takes a compensatory increase in the activity of LDL receptors and consequently accelerate the catabolism of cholesterol (Xc) LDL.

Lipid-lowering effect of statins is associated with a reduction in total cholesterol by LDL-C. Lowering LDL cholesterol is dose-dependent and is not linear, and the exponential nature.

Statins do not affect the activity of lipoprotein lipase and hepatic, no significant effect on the synthesis and catabolism of free fatty acids, so their impact on the level of a second Tg and indirectly through their major effects on the reduction of LDL-C. A moderate reduction in triglycerides in the treatment of statins, apparently, associated with expression remnantnyh (apo E) receptors on the surface of hepatocytes, involved in the catabolism of LPPP, a composition which approximately 30% TG.

According to controlled studies, lovastatin increases the level of HDL-C to 10%.

In addition to lipid-lowering action, Statins have a positive impact in the endothelial dysfunction (preclinical signs of early atherosclerosis), on the vascular wall, state of atheroma, improve the rheological properties of blood, have antioxidant, antiproliferative properties.

Pharmacokinetics

When taken orally, lovastatin slowly and incompletely (about 30% the dose) absorbed from the gastrointestinal tract. Taking on an empty stomach reduces absorption by 1/3. C_max It reached within 2-4 no, then the plasma level decreases rapidly, making up through 24 no 10% from the maximum. Plasma protein binding – 95%. C_ss lovastatin and its active metabolites with a single appointment at night is achieved by 2-3 day of therapy and in 1.5 times higher, than after a single dose.

Lovastatin crosses the BBB and the placental barrier. Subjected to intensive metabolism in the “first pass” through the liver, oxidized to beta hydroxy acid, its 6-hydroxy derivative and other metabolites, some of which are pharmacologically active (block 3-hydroxy-3-methylglutaryl-coenzyme A-reductase). T_1/2 – 3 no. It is excreted through the intestines 83%, 10% – kidney.

Testimony

Primary hypercholesterolemia (hypolipoproteinemia IIa and IIb types) high in LDL (with the ineffectiveness of diet therapy in patients at increased risk of coronary atherosclerosis), combined giperholesterinemia and gipertriglitzeridemia, atherosclerosis.

Dosage regimen

Is the inside. The initial dose – 10-20 mg 1 once / day in the evening during meals. Increase the dose if necessary 1 once every 4 of the week.

The maximum daily dose: 80 mg 1 or 2 admission (during breakfast and dinner). In the case of a decrease in concentration in plasma Xc to 140 mg / dL (3.6 mmol / l) or Hs-LPNP to 75 mg / dL (1.94 mmol / l) the dose of lovastatin should be reduced.

In an application with drugs, suppressive immunity, the daily dose of lovastatin should not exceed 20 mg.

Side effect

From the digestive system: heartburn; rarely – nausea, diarrhea, constipation, flatulence, dry mouth, taste disturbances, anorexia, increased activity of hepatic transaminases in the blood, in a few cases – cholestatic jaundice, hepatitis, pancreatitis, gastralgia, abnormal liver function.

On the part of the musculoskeletal system: mialgii, myopathies, myositis, raʙdomioliz (while using cyclosporine, gemfibrozil or nicotinic acid), artralgii, increase in the content of extracardial fraction of CPK in blood plasma.

From the central and peripheral nervous system: dizziness, headache, sleep disorders, convulsions, paresthesia; in a few cases – mental disorders.

From the hematopoietic system: gemoliticheskaya anemia, leukopenia, thrombocytopenia.

On the part of the organ of vision: blurred vision, cataract, Cataract, optic atrophy.

Allergic reactions: skin rash, itch; in a few cases – hives, angioedema, toxic epidermal necrolysis.

Other: reduced potency; acute renal failure (due to rhabdomyolysis), chest pain, heartbeat.

Contraindications

Acute liver disease, increased activity of hepatic transaminases in serum of unknown etiology, pregnancy (or its probability), lactation (breast-feeding), severe general condition of the patient, hypersensitivity to lovastatin.

Pregnancy and lactation

Lovastatin is contraindicated for use during pregnancy and lactation. (breast-feeding).

Cautions

Use with caution in patients with a history of liver disease, as well as with chronic alcoholism.

Lovastatin should be discontinued in the event of a persistent increase in the blood levels of hepatic transaminases and / or CPK, as well as in the general serious condition of the patient due to any disease.

Drug Interactions

With simultaneous use with antibiotics of the macrolide group, gemfibrozilom, immunosuppressants (incl. Cyclosporin), nicotinic acid increases the risk of rhabdomyolysis with the subsequent development of acute renal failure (especially in patients with diabetic nephropathy).

While the use of anticoagulants, with coumarin and indandione derivatives, there is an increase in bleeding and an increase in prothrombin time.

When used simultaneously with oral contraceptives, lovastatin can prevent hyperlipidemia, due to the use of hormonal contraceptives.

It is believed, that it is possible to reduce the hypolipidemic effect of lovastatin while using “loop” and thiazide diuretics.

Diltiazem, verapamil, isradipine inhibits the CYP3A4 isoenzyme, which is involved in the metabolism of lovastatin, therefore, with simultaneous use, it is possible to increase the concentration of lovastatin in the blood plasma and increase the risk of developing myopathy.

There are reports of the development of acute rhabdomyolysis and hepatotoxicity with simultaneous use with itraconazole.

A case of the development of severe hyperkalemia in a patient with diabetes mellitus with the simultaneous use of lisinopril is described.