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

Excipients: corn starch, microcrystalline cellulose, silicon dioxide colloid (aerosil), magnesium stearate, bugyl hydroxy anisole, milk sugar (lactose).

Description:Round tablets of flat-cylindrical form of white with a yellowish shade of color, with a bevel.

Pharmacotherapeutic group:Hypolipidaemic agent - HMG-CoA reductase inhibitor

ATX: & nbsp

C.10.A.A.02 Lovastatin

C.10.A.A Inhibitors of HMG-CoA reductase

Pharmacodynamics:Lovastatin is an inhibitor of endogenous cholesterol synthesis in the liver. In organism, lovastatin, in the form of an inactive lactone, is directly hydrolyzed to the corresponding βhydroxy acid - therapeutically active form. This active form acts as a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), an enzyme that catalyzes the conversion of HMG-CoA into mevalonate, the initial stage of cholesterol biosynthesis.Effective in reducing total cholesterol in the blood and cholesterol in low density lipoprotein (LINC) and very low density lipoprotein (VLDL). It also reduces the content of apolipoprotein B, the concentration of triglycerides in the blood plasma and moderately increases the concentration of high-density lipoprotein (HDL). Other effects of lovastatin (improving endothelial function, stabilizing plaques, anti-inflammatory and antithrombogenic effect), some of which are not directly related to the effect of lipid lowering, contribute to the antiatherosclerotic effect of lovastatin. The pronounced therapeutic effect of the drug manifests itself within 2 weeks, and the maximum - 4-6 weeks from the start of treatment and is maintained for 4-6 weeks after the withdrawal of therapy. The efficacy of lovastatin for long-term use (up to 5 years) does not decrease.

Pharmacokinetics:

In the gastrointestinal tract (GIT) is absorbed slowly and not completely - about 30% of the dose taken, taking an empty stomach reduces absorption by 1/3 compared with the reception with food. Time to reach the maximum concentration (T_Сmах) - 2-4 hours, the maximum concentration (C_max ) - 7.8 ng / ml for lovastatin and 11.9 ng / ml for beta hydroxy acid, then the plasma concentration decreases rapidly, accounting for 24% 10% of the maximum. Connection with blood plasma proteins - 95%. The clearance of lovastatin and its active metabolites with a single appointment for the night is achieved by 2-3 days. and 1.5 times higher than after a single dose. Penetrates through the blood-brain barrier (GEB) and the placental barrier.

It is subjected to intensive metabolism during the "first passage" through the liver, it is oxidized to beta-hydroxy acid, its 6-hydroxy derivative and other metabolites, some of which are pharmacologically active (blocking HMG-CoA reductase). In the metabolism of the drug, isozymes CYP3A4, CYP3A5 and CYP3A7 are involved.

Half-life (T_1/2) - 3 hours. Output through the intestine - 83%, kidneys -10%.

Indications:

- To reduce elevated serum levels of total cholesterol, LDL cholesterol and triglycerides in the serum of patients with primary hypercholesterolemia (Pa and Fb types according to Fredrickson), including familial heterozygous hypercholesterolemia, polygenic hypercholesterolemia, and mixed hyperlipidemia. The drug is prescribed with insufficient effectiveness of diet therapy and other non-medicamentous measures.

- Treatment of coronary atherosclerosis in patients with ischemic heart disease (IHD) in order to slow its progression.

Contraindications:

- Increased individual sensitivity to lovastatin or other components of the drug;

- liver disease in the active phase or persistent increase in the activity of "liver" transaminases of unclear etiology;

- pregnancy and lactation;

- age under 18 years (efficiency and safety not established)

- lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

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

Pregnancy and lactation:

The drug is contraindicated for use in pregnancy and lactation. During the period of drug treatment Lovastatin, women of reproductive age should use reliable contraceptives.

It is not known whether lovastatin with breast milk. Therefore, if taking the drug during this period is necessary, then breastfeeding should be canceled.

Dosing and Administration:

Inside, during a meal. Before prescribing the drug, and also during its use, the patient should be prescribed a standard hypocholesterolemic diet.

- Hyperlipidemia

The recommended dose of Lovastatin is 10 to 80 mg once daily. Usually, the initial dose in patients with moderate hypercholesterolemia is 20 mg once a day during an evening meal; in patients with severe hypercholesterolemia (total cholesterol in the blood plasma is more than 7.8 mmol / l) - 40 mg / day. If necessary, to achieve the target values of serum cholesterol, the dose of the drug Lovastatin can be increased to a maximum daily dose of 80 mg per day in one or more doses (during breakfast and dinner).Changes (selection) of the dose should be carried out at intervals of not less than 4 weeks. If the concentration of total cholesterol in the blood plasma drops to 140 mg / 100 ml (3.6 mmol / L) or LDL-cholesterol to 75 mg / 100 ml (1.94 mmol / l), the dose should be reduced. If the patient simultaneously takes ciclosporin, fibrate shi nicotinic acid (more than 1 g per day) - the maximum daily dose of the drug Lovastatin should not exceed 20 mg / day.

Lovastatin in a dose above 20 mg / day. in patients with severe renal insufficiency (creatinine clearance (CK) less than 30 ml / min and / or 0.5 ml / sec) should be taken with extreme caution and under control.

- Coronary atherosclerosis

Daily doses range from 20 to 80 mg once or divided into 2 doses. Dosage and duration of administration are determined by the physician.

Side effects:

A drug Lovastatin, as a rule, patients are well tolerated.

From the digestive system: often - heartburn, nausea, abdominal pain, constipation or diarrhea, flatulence, indigestion; very rarely - dry mouth, taste perversion, biliary cholestasis, hepatitis, gastralgia, cholestatic jaundice, hepatic dysfunction, hepatitis, acute pancreatitis.

From the central and peripheral nervous system: often - headache, dizziness; very rarely - peripheral neuropathy, sleep disorders, general weakness, insomnia, paresthesia, mental disorders (including anxiety).

From the musculoskeletal system: often - myalgia, muscle cramps; rarely - myopathy, myositis, dermatomyositis; very rarely - in patients taking both ciclosporin, gemfibrozil or nicotinic acid increased the risk of rhabdomyolysis.

From the hematopoiesis: hemolytic anemia, leukopenia, thrombocytopenia.

From the side of the organ of vision: very rarely - "fog" before the eyes, clouding of the lens, cataracts, atrophy of the optic nerve.

Laboratory indicators: moderate increase in the activity of "hepatic" transaminases: alanine aminotransferase (ALT) and asparagine aminotransferase (ACT) (including a threefold increase relative to the upper limit of the norm - in 1.5% of cases); rarely - increased activity of creatine phosphokinase (CK); very rarely - increased alkaline phosphatase and bilirubin.

Allergic reactions: very rarely - the syndrome of hypersensitivity (anaphylaxis, lupus-like syndrome, arthralgia, angioedema, hives,erythema multiforme, including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), skin rash, itching.

Other: Very rarely - reduced potency, acute renal failure (due to rhabdomyolysis), chest pain, palpitations, alopecia.

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: cancellation 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 activity of CK. There is no specific antidote, hemodialysis is not effective.

Interaction:

Simultaneous reception of the drug Lovastatin and nicotinic acid (more than 1 g / day), cyclosporine, macrolide antibiotics (erythromycin, clarithromycin), "azole" antifungal agents (ketoconazole, itraconazole), HIV protease inhibitors (ritonavir), nefazodone may lead to an increase in the concentration of lovastatin in the blood plasma, resulting in myopathy with rhabdomyolysis and renal insufficiency.Grapefruit juice in large amounts (more than 1 liter / day) increases Cmax and the area under the concentration-time curve (AUC) of lovastatin and the risk of myopathy. Simultaneous reception of the drug Lovastatin with derivatives of fibrolic acid (gemfibrozil, fenofibrate and others) can also lead to the development of myopathy, although the mechanism is unclear in this case.

Co-administration of the drug Lovastatin and warfarin can enhance the influence of the latter on the parameters of blood coagulability in connection with which, the risk of bleeding may increase. In the case of joint administration of these two drugs, it is recommended that the prothrombin time be determined with an appropriate frequency until the stable digits of this index are reached. Kolestyramine and colestipol reduce bioavailability (the use of lovastatin is possible in 2-4 hours after taking these drugs, with an additive effect noted).

Special instructions:

Treatment with drug Lovastatin should be accompanied by an appropriate diet (low in cholesterol).

Drug therapy Lovastatin can cause an increase in the activity of "hepatic" enzymes.This increase, as a rule, is small and clinically insignificant. However, it is recommended to monitor enzyme levels before the start of therapy and during the course of treatment at regular intervals (for 1 year, then at least once every 6 months).

When the activity of ACT and / or ALT in the blood serum increases 3 times relative to the upper limit of the norm, the drug treatment Lovastatin must be terminated. Treatment with the drug should be discontinued in the event of a persistent increase in the activity of CK. This should be taken into account in the differential diagnosis of chest pain. Drug therapy Lovastatin can lead to the development of myopathy, and as a result, to rhabdomyolysis and renal failure. The risk of this pathology increases in patients receiving simultaneously one or more of the following medicines: fibrates (gemfibrozil, fenofibrate), ciclosporin, nefazodone, macrolides (erythromycin, clarithromycin), antifungal agents from the group of "azoles" (ketoconazole, itraconazole) and HIV protease inhibitors (ritonavir). The risk of developing myopathy is also increased in patients with severe renal failure.

Patients should inform the doctor in case of unexplained tenderness in the muscles, especially if accompanied by malaise or fever.

Care should be taken when using the drug Lovastatin in patients who consume excessive amounts of alcohol, and in patients with a history of liver disease.

During the period of drug treatment Lovastatin, women of reproductive age should use reliable contraceptives.

Lovastatin is less effective in patients with rare homozygous familial hypercholesterolemia, probably because these patients lack functional LDL receptors. Apparently, in such patients Lovastatin faster able to increase the activity of "liver" transaminases.

Lovastatin has only moderate effects on the reduction of triglyceride levels and is not indicated in cases where the main pathology is hypertriglyceridemia (i.e., Fredrickson I, IV and V type hyperlipidemia).

Effect on the ability to drive transp. cf. and fur:There was no impact on the ability to drive a car or work with technical devices.

Form release / dosage:Tablets of 20 mg and 40 mg.

Packaging:

For 10, 15 or 20 tablets per contour cell package.

For 2 or 3 contour packs of 10 tablets with instructions for use are put in a cardboard box.

2 contour cell packs of 15 tablets with a dosage of 40 mg with instructions for use are placed in a cardboard pack.

On 1 circuit cell pack of 20 tablets with instructions for use are placed in a cardboard pack.

Storage conditions:

In a dry place at a temperature of no higher than 25 ° C.

In a place inaccessible to children.

Shelf life:

2 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-007837/09

Date of registration:06.10.2009

Expiration Date:Unlimited

The owner of the registration certificate:LEKFARM, SOOO LEKFARM, SOOO Republic of Belarus

Manufacturer: & nbsp

LEKFARM, SOOO Republic of Belarus

Representation: & nbspРомфарма ОООРомфарма ООО

Information update date: & nbsp12.04.2018

Illustrated instructions

Instructions

Lovastatin (Lovastatin)