Lovastatin

General characteristics. Structure:

Active ingredient: 20 mg or 40 mg of a lovastatin.

Excipients: starch corn, cellulose microcrystallic, aerosil, magnesium stearate, бутилгидроксианисол, lactose.

Hypolipidemic means. Lovastatin breaks synthesis of cholesterol in a liver, strengthens its catabolism. Therapy lovastatiny does not lead to accumulation of toxic sterol.

Pharmacological properties:

Pharmacodynamics. Hypolipidemic means. Lovastatin breaks the first stage of synthesis of cholesterol in a liver – formation of mevalonovy acid. In an organism ловастатин it is hydrolyzed to an active form – beta hydroxyacid which inhibits 3-gidroksi-3-metilglutaril-SOA-reduktazu and breaks transformation GMG-SOA into mevalonovy acid therefore cholesterol synthesis decreases, its catabolism amplifies. Reduces the content in blood of lipoproteids of very low density, lipoproteids of low density and triglycerides, moderately increases the maintenance of lipoproteids of high density.

As conversion GMG-SOA in mevalonovy acid is an early stage of synthesis of cholesterol, therapy lovastatiny does not lead to accumulation of toxic sterol.

At reception of medicine of 1 times/days the prodozhitelnost of action makes 24 h. After cancellation at course reception effect of drug remains for 4-6 weeks.

Pharmacokinetics. After intake the maximum concentration in a blood plasma is reached in 2-4 hours. At administration of drug on an empty stomach extent of absorption decreases by 30% in comparison with inclusion in food time. Linkng with proteins of plasma makes 95%. Lovastatin gets through a blood-brain barrier and a placental barrier. It is metabolized in a liver with formation of several metabolites, including pharmacological active metabolite – beta hydroxyacid. It is removed with bile – 83% and with urine – 10%.

At a research of patients with a heavy renal failure (the clearance of creatinine makes 10-30 ml/min.), concentration in a blood plasma of total number of inhibitors after a single dose of a lovastatin it was approximately twice higher, than at healthy volunteers.

Concentration of a lovastatin in a blood plasma at elderly people (at the age of 70-78 years) is higher (Cmax approximately for 45%), than at adult patients of young age (18-30 years).

Indications to use:

Route of administration and doses:

The initial dose at a hypercholesterolemia makes 10 - 20 mg of 1 times a day, at atherosclerosis – 20 - 40 mg of 1 times a day. Drug is accepted during a dinner.

If necessary in 4 weeks the dose is increased to 80 mg in 1 or 2 receptions – during a breakfast and a dinner.

For the patients receiving immunodepressive therapy and patients with a heavy renal failure (clearance of creatinine less than 30 ml/min.) the maximum daily dose makes 20 mg.

In case of decrease in concentration in a blood plasma of the general cholesterol to 140 mg / 100 ml (3,6 mmol/l) or lipoproteids of low density to 75 mg / 100 ml (1,94 mmol/l) a dose should be reduced.

Features of use:

Lovastatin, as well as other inhibitors of GMG-KOA-reduktazy, can cause a myopathy (muscle pain, morbidity and weakness in muscles with increase in a creatine kinase are ten times higher than the upper bound of norm). The myopathy sometimes takes the form of a rabdomioliz with/without acute a renal failure with emergence as a result of it a myoglobinuria, and is rare – death. The risk of a myopathy increases due to increase in the inhibiting activity concerning GMG-KOA-reduktazy in a blood plasma.

The risk of development of a myopathy / рабдомиолиза depends on a drug dose. All patients beginning treatment lovastatiny or whose dose of a lovastatin increases, have to be warned about risk of emergence of a myopathy and about need to report quickly about any inexplicable muscle pains, morbidity and weakness in muscles. In the presence of the confirmed or estimated myopathy treatment lovastatiny has to be immediately stopped. In most cases, at the bystry termination of treatment muscular symptoms vanish, and creatine kinase level is normalized. Periodic determination of level of a creatine kinase can be appointed to the patients who began therapy lovastatiny or whose dose increases that does not guarantee prevention of a myopathy. Many patients at whom developed рабдомиолиз at treatment lovastatiny had difficult case histories, including a renal failure which usually is a consequence of a long diabetes mellitus. Such patients deserve more careful monitoring. At increase in the KFK level treatment lovastatiny needs to be stopped.

Treatment lovastatiny should be cancelled temporarily if the patient tests the acute or serious diseases contributing to development of a renal failure, secondary in relation to a rabdomioliz, for example, sepsis, hypotension, heavy operations, injuries, heavy metabolic, endocrine or electrolytic disturbances, or uncontrollable epilepsy.

The risk of development of a myopathy / рабдомиолиза increases at simultaneous use of a lovastatin with the following drugs:
- strong CYP3A4 inhibitors: increase the level of a lovastatin in plasma that increases risk of development of a myopathy. Makrolidny antibiotics erythromycin and кларитромицин, an antibiotic of a ketolidny row телитромицин, HIV protease inhibitors, боцепревир, телапривир and antidepressant нефазодон belong to such drugs интраконазол, кетоконазол, посаконазол. The combination of these drugs with lovastatiny is contraindicated! In need of performing therapy by these drugs, reception of a lovastatin during a course of treatment has to be stopped.

In vitro was proved that вориконазол inhibits metabolism of a lovastatin, increases concentration of a lovastatin in plasma owing to what it is recommended to adjust doses of a lovastatin at simultaneous use with vorikonazoly.

- gemfibrozit: sharing with lovastatiny it is necessary to avoid.
- other gipolipedimechesky drugs (fibrata or niacin in a dose> 1 g/days): it is necessary to be careful at purpose of fibrat or niacin in hypolipidemic doses (> 1 g/day) with lovastatiny since these drugs can lead to a myopathy at monotherapy. It is necessary to weigh carefully odidayemy advantage of possible risk at the combined use of a lovastatin with fibrata or niacin.
- cyclosporine: joint reception should be avoided.
- даназол, diltiazem, verapamil with high doses of a lovastatin: the dose of a lovastatin should not exceed 20 mg at joint reception.
- Amiodaronum: the dose of a lovastatin should not exceed 40 mg a day at the patients receiving the accompanying treatment by Amiodaronum. It is possible to apply ловастатин in a dose higher than 40 mg a day with Amiodaronum if the clinical effect exceeds the increased risk of development of a myopathy. The risk of development of a myopathy / рабдомиолиза increases when Amiodaronum is used along with high doses of inhibitors of GMG-KOA-reduktazy.
- colchicine: at joint reception myopathy cases / рабдомиолиза were registered, it is necessary to show care at purpose of a lovastatin with colchicine.
- ранолазин: the risk of a myopathy / рабдомиолиза can be increased at simultaneous use, dose adjustment is necessary.

It is necessary to control the level of activity of transaminases and other enzymes of a liver in blood serum prior to therapy by statines and according to clinical indications of the Second World War ремя uses. In the presence of the serious damages of a liver with clinical symptoms and/or a hyperbilirubinemia, jaundice appearing during reception, use of statines needs to be stopped. If other reason of development of serious damage of a liver is not established, use of statines should not be resumed. With care appoint at liver diseases in the anamnesis, an alcoholism, the organ transplantation accompanying immunodepressive therapy, a chronic renal failure, urgent surgical manipulations (including stomatologchiyesky).

Messages on very exceptional cases developments of intersticial diseases of lungs at reception of statines were gained, especially at long therapy. At emergence of symptoms of intersticial diseases of lungs, such as breath disturbance, short wind, unproductive cough, deterioration in the general state (fatigue, loss of weight, fever), therapy by statines should be stopped.

Statines as a class increase glucose level in blood, and with high risk of development of diabetes can cause increase in level of sugar in blood which demands the corresponding treatment in patients. However advantages of statines concerning decrease in risks of cardiovascular diseases exceeds small uvelichesny development of diabetes of risk therefore it is not necessary to stop use of statines. Periodic monitoring of a glycemia at patients from risk group (a klyukoz on an empty stomach of 5,6-6,9 mmol/l, a body weight index> 30 kg/sq.m, increase in level of triglycerides, hypertensia), according to the existing recommendations is necessary.

Joint use of grapefruit juice with drug can lead to increase in concentration of a lovastatin in a blood plasma therefore the patients accepting drug have to avoid the grapefruit juice use.

With care apply at patients with rare hereditary diseases: inborn galactosemia, deficit of lactase, glucose/galactose sprue.

Patients should be warned about substances which should not be accepted along with lovastatiny and to advise immediately to report about inexplicable muscular pains, morbidity or weakness in muscles. Patients need to recommend to inform other doctors appointing new medicine that they accept ловастатин.

Safety at pregnant women is not established. Medicine is contraindicated at pregnancy and in the period of a lactation. The pregnant or planning pregnancy women should not use medicine. In case of pregnancy approach reception of a lovastatin should be stopped immediately. Lovastatin women of childbearing age can appoint if the probability of pregnancy is reliably excluded, and the patient is informed on potential danger. There are no data on allocation of a lovastatin with breast milk. Considering a possibility of undesirable reactions at babies, the women receiving this drug have to stop feeding by a breast.

During treatment it is necessary to be careful during the driving of motor transport and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

From the alimentary system: heartburn; seldom - nausea, diarrhea, a lock, a meteorism, dryness in a mouth, taste disturbances, anorexia, increase in activity of hepatic transaminases in blood, in isolated cases - cholestatic jaundice, hepatitis, pancreatitis, a gastralgia, an abnormal liver function.

From a musculoskeletal system: mialgiya, myopathies, a miositis, рабдомиолиз (at simultaneous use of cyclosporine, a gemfibrozil or niacin), arthralgias, increase the maintenance of the KFK noncardiac fraction in a blood plasma.

From TsNS and peripheral nervous system: dizziness, headache, sleep disorders, spasms, paresthesias; in isolated cases - mental disturbances.

From system of a hemopoiesis: hemolitic anemia, leukopenia, thrombocytopenia.

From an organ of sight: sight misting, phacoscotasmus, cataract, atrophy of an optic nerve.

Allergic reactions: skin rash, itch; in isolated cases - a small tortoiseshell, a Quincke's edema, a toxic epidermal necrolysis.

Others: decrease in a potentiality; the acute renal failure (caused rabdomiolizy), thorax pain, heartbeat.

Interaction with other medicines:

Interaction with CYP3A4 isoenzyme inhibitors. Lovastatin is metabolized by CYP3A4 isoenzyme, but has no the inhibiting activity in the relation of this isoenzyme therefore ловастатин cannot lead to increase in concentration in plasma of other drugs which are metabolized CYP3A4. Joint reception of strong CYP3A4 inhibitors (интраконазол, кетоконазол, посаконазол, кларитромицин, телитромицин, HIV protease inhibitors, боцепревир, телапревир, нефазодон and erythromycin) with lovastatiny is contraindicated in connection with increase in risk of a myopathy because of reduction in the rate of removal of a lovastatin. In vitro вориконазол inhibits metabolism of a lovastatin. At their simultaneous use it is recommended to adjust doses of a lovastatin to reduce risk of development of a myopathy / рабдомиолиза.

Interaction with hypolipidemic drugs which can cause a myopathy at monotherapy. The risk of development of a myopathy also increases at use of hypolipidemic drugs which are not strong CYP3A4 inhibitors, but which can lead to a myopathy at monotherapy.

Cyclosporine, gemfibrozit: the risk of development of a myopathy / рабдомиолиза increases at simultaneous use of cyclosporine or a gemfibroliz with lovastatiny. It is necessary to avoid joint reception of these drugs.

Danazol, diltiazem or verapamil: the risk of development of a myopathy / рабдомиолиза increases at simultaneous use of a danazol, dilteazem or verapamil, especially with higher doses of a lovastatin. The dose of a lovastatin should not exceed 20 mg a day at joint reception with danazoly, diltiazem or verapamil.

Amiodaronum: the risk of development of a myopathy / рабдомиолиза increases at use of Amiodaronum along with other drugs of a statinovy row (GMG-KOA-reduktazy inhibitors). The dose of a lovastatin should not exceed 40 mg a day at joint reception with Amiodaronum.

Coumarinic anticoagulants: it is recommended to define a prothrombin time at the patients accepting anticoagulants before beginning treatment lovastatiny, and often it is enough to define a prothrombin time at the beginning of therapy to guarantee that no essential changes will happen. As soon as the stable level of an indicator of a prothrombin time is reached, its further control should be carried out bucketed, recommended for the patients receiving therapy by anticoagulants. At change of a dosage of a lovastatin it is also necessary to carry out control of a prothrombin time according to the above scheme. Therapy lovastatiny does not cause changes of a prothrombin time and risk of bleedings in the patients who are not accepting anticoagulants.

Colchicine: myopathy cases, including рабдомиолиз, were registered at combined use of colchicine with lovastatiny.

Ranolazin: the risk of a myopathy, including рабдомиолиз, can be increased by simultaneous use of a ranolazin with lovastatiny.

Propranolol: healthy volunteers had no clinically significant pharmacokinetic or pharmakodinamichesky interactions at co-administration of single doses of a lovastatin and propranol.

Digoxin: at patients with a hypercholesterolemia at a concomitant use is a lovastatin and digoxin concentration of digoxin in plasma did not change.

Peroral hypoglycemic drugs: in pharmacokinetic researches at patients with giperkholesterinemichesky non-insulin-dependent diabetes ловастатин did not interact with drugs глипизид or Chlorproramidum.

Endocrine function: patients with endocrine dysfunction or the accepting drugs influencing activity of endogenous steroid hormones at joint reception with lovastatiny need medical monitoring.

Contraindications:

Acute diseases of a liver, continuous increase in activity of hepatic transaminases of not clear genesis, cholestasia, pregnancy, the lactation period, age up to 18 years.

Overdose:

Symptoms: the overdose is followed by strengthening of side effects.

Treatment: control of function of a liver, symptomatic therapy.

Storage conditions:

In the place protected from moisture at a temperature not above 25 °C. List B. To store in the place, unavailable to children. Period of validity 3 years.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in a blister strip packaging. On two or three blister strip packagings on 10 tablets in a pack.