Холетар - instructions for use, doses, side effects, contraindications

Lactose monohydrate, pregelatinized starch, butyl hydroxy anisole, dye blue, patented V, E131, quinoline yellow dye, E104 *, corn starch, microcrystalline cellulose, magnesium stearate.

* - for tablets of 40 mg.

Description:

Tablets of 20 mg: round, slightly biconvex tablets of light blue color with impregnations on the surface and in the mass of the tablet, with a facet and a risk on one side.

Tablets 40 mg: round, slightly biconvex tablets of light green color with impregnations on the surface and in the mass of the tablet, with a facet and a risk on one side.

Pharmacotherapeutic group:lipid-lowering 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 β-hydroxy acid, a 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.

Highly effective in reducing total cholesterol in the blood and cholesterol in low density lipoprotein (LDL) 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 (improved endothelial function, plaque stabilization, 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 expressed therapeutic effect of the drug manifests itself within 2 weeks, and the maximum - in 4-6 weeks from the start of treatment. The efficacy of lovastatin for long-term use (up to 5 years) does not decrease.

Pharmacokinetics:

In the gastrointestinal tract lovastatin absorbed slowly and not completely - about 30% of the dose. Lovastatin should be taken with food, since taking the drug on an empty stomach, its concentration in the plasma is one-third lower than when taken with food. The maximum therapeutic concentration is achieved in 2-4 hours, then the concentration in the blood plasma rapidly decreases, making after 24 hours 10% of the maximum. Connection with blood plasma proteins - 96-98,5%. The equilibrium concentration of 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 through blood-brain and placental barriers.

It is subjected to intensive metabolism at the "first passage" through the liver. The main metabolites are formed due to the oxidation of lactone with the participation of cytochrome P450 (CYP3A4).

The half-life (T_1/2) - 3-4 hours.Output through the intestine - 83% and kidneys - 10%.

Indications:

- To reduce elevated serum levels of total cholesterol, LDL cholesterol and triglycerides in serum in patients with primary hypercholesterolemia (types IIa and IIb by 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 "hepatic" transaminases of unclear etiology;

- pregnancy and lactation;

- age to 18 years (efficacy and safety not established).

Carefully:

Diseases of the liver (in the anamnesis), chronic alcoholism, organ transplantation, concomitant immunosuppressive therapy, chronic renal failure (CRF), urgent (urgent) surgical manipulations (including dental), with simultaneous admission with gemfibrozil, fenofibrate, etc.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 during pregnancy and lactation. During the treatment with Holetar®, women of reproductive age should use reliable contraception.

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 a day.

Usually 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 level The dose of Holetar® can be increased to the maximum daily dose 80 mg per day in one or more receptions (during breakfast and dinner). Changes (selection) of the dose should be carried out at intervals of not less than 4 weeks.

If the plasma concentration of total cholesterol is reduced 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, fibrates or nicotinic acid (more than 1 g per day) - the maximum daily dose of Holetar ® should not exceed 20 mg / day.

Holetar® at a dose above 20 mg / day in patients with severe renal insufficiency (creatinine clearance (CC) less than 30 ml / min and / or 0.5 ml / s) should be taken with extreme caution and monitoring.

Coronary atherosclerosis

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

Side effects:

Classification of the incidence of adverse events (WHO):

very often -> 1/10

often from> 1/100 to <1/10

infrequently - from> 1/1000 to <1/100

rarely from> 1/10000 to <1/1000

very rarely - from <1/10000, including individual messages.

The drug Holletar®, as a rule, is well tolerated by patients.

On the part of the organs of 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 (CNS) and peripheral nervous system: often - headache, dizziness; very rarely - peripheral neuropathy, sleep disorders, general weakness, insomnia, paresthesia, mental disorders (including anxiety).

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

On the part of the organs of hematopoiesis: very rarely - as a manifestation of hypersensitivity syndrome (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: a moderate increase in the activity of "hepatic" transaminase: 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 (CKF); very rarely - increased alkaline phosphatase and bilirubin.

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

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: removal of the drug, common activities: monitoring and maintenance of vital functions, preventing further absorption of the drug (gastric lavage, administration of activated charcoal or laxatives) to monitor liver function.With the development of myopathy with rhabdomyolysis and acute renal insufficiency, intravenous administration of sodium hydrogencarbonate solution and diuretic is necessary, with hyperkalemia - intravenous administration of calcium chloride or calcium gluconate solution, glucose infusion with insulin; in severe cases - hemodialysis.

Interaction:

Simultaneous reception of Holetar® and nicotinic acid (more than 1 g / day), cyclosporine, macrolide antibiotics (erythromycin, clarithromycin), "azole" antifungal drugs (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 quantities (more than 1 liter / day) increases the maximum concentration in the plasma (FROM_mOh) and the area under the curve "concentration-time" (AUC) lovastatin and the risk of myopathy.

Simultaneous reception of preparation Holetar® with derivatives of fibroic acid (gemfibrozil, fenofibrate and others) can also lead to the development of myopathy, although the mechanism is unclear in this case.

Co-administration of Holetar® and warfarin can increase the effect of the drug on blood clotting parameters, which may increase the risk of bleeding. 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 h after administration of these drugs, with an additive effect noted).

Special instructions:

Treatment with Holetar® should be accompanied by a suitable diet (with low cholesterol content).

Therapy with Holetar® 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).

With increasing content ACT and / or ALT in the serum, the treatment with Holetar® should be discontinued three times the upper limit of the norm.

Treatment with the drug should be stopped in case of persistent increase in the activity of creatine phosphokinase (CK). This should be taken into account in the differential diagnosis of chest pain.

Therapy with the drug Holletar® 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 their physician in time if there is an unexplained pain in the muscles, especially if it is accompanied by a malaise or fever.

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

During the treatment with Holetar®, women of reproductive age should use reliable contraception.

Choletar® is less effective in patients with rare homozygous familial hypercholesterolemia, probably because these patients lack functional LDL receptors. Apparently, in such patients, Holletar® is more likely to increase the activity of "liver" transaminases.

Lovastatin has only a moderate effect on reducing triglyceride levels and is not indicated in cases where the main pathology is hypertriglyceridemia (i.e., hyperlipidemia I, IV and V types by Fredrickson).

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, 20 mg and 40 mg.

Packaging:

10 tablets per blister.

For 2 or 3 blisters per pack of cardboard along with instructions for use.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N014638 / 01

Date of registration:29.08.2008

Expiration Date:Unlimited

Date of cancellation:2016-12-09

The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Manufacturer: & nbsp

VECTOR-MEDICA, CJSC Russia

KRKA, d.d. Slovenia

Representation: & nbspKRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Information update date: & nbsp09.12.2016

Illustrated instructions

Instructions

Holetar® (Choletar®)