Cardiostatin^® (Tablets) Instructions for Use

Marketing Authorization Holder

Nizhpharm JSC (Russia)

Manufactured By

Makiz-Pharma, LLC (Russia)

Or

Chemopharm, LLC (Russia)

ATC Code

C10AA02 (Lovastatin)

Active Substance

Lovastatin (Rec.INN WHO registered)

Dosage Forms

	Cardiostatin®	Tablets 20 mg: 30 pcs.
		Tablets 40 mg: 30 pcs.

Dosage Form, Packaging, and Composition

Tablets are flat-cylindrical, white or almost white, with a bevel and a score line.

Excipients: lactose, pregelatinized potato starch, microcrystalline cellulose, croscarmellose sodium, butylhydroxyanisole, calcium stearate.

10 pcs. – contour cell blisters (3) – cardboard packs.
30 pcs. – contour cell blisters (1) – cardboard packs.

Clinical-Pharmacological Group

Hypolipidemic agent

Pharmacotherapeutic Group

Hypolipidemic agent – HMG-CoA reductase inhibitor

Pharmacological Action

Hypolipidemic drug. Inhibitor of endogenous cholesterol synthesis. Disrupts the early stages of cholesterol synthesis in the liver.

In the body, Lovastatin forms a free beta-hydroxy acid, which competitively inhibits HMG-CoA reductase and disrupts its conversion to mevalonate, resulting in decreased cholesterol synthesis and increased cholesterol catabolism.

It reduces the content of triglycerides, LDL, VLDL in blood plasma and moderately increases the content of HDL. It significantly reduces the amount of apolipoprotein B, which is part of LDL, and other circulating components of LDL.

A pronounced therapeutic effect of the drug is observed within 2 weeks of treatment, the maximum effect is achieved 4-6 weeks after the start of treatment.

Cardiostatin^® is effective in primary hypercholesterolemia in patients with uncomplicated compensated diabetes mellitus type 1 and 2.

Pharmacokinetics

Absorption

Absorbed slowly and incompletely from the gastrointestinal tract – about 30% of the administered dose; taking on an empty stomach reduces absorption by 30%. C_max in blood plasma is noted after 2-4 hours, then the level in blood plasma decreases rapidly, amounting to 10% of the maximum after 24 hours.

Distribution

Plasma protein binding is 95%. The clearance of lovastatin and its active metabolites with a single nighttime administration is achieved on the 2nd-3rd day of therapy and is 1.5 times higher than after a single dose. Penetrates the blood-brain barrier and the placental barrier.

Metabolism

It undergoes intensive metabolism during the “first pass” through the liver, is oxidized to a beta-hydroxy acid, its 6-hydroxy derivative and other metabolites, some of which are pharmacologically active (block 3-hydroxy-3-methylglutaryl-coenzyme A reductase).

Excretion

T_1/2 is 3 hours. Excreted through the intestine – 83%, by the kidneys 10%.

Indications

• Primary hypercholesterolemia (type IIa and IIb) with high LDL content (not corrected by special diet and physical activity);
• Combined hypercholesterolemia and hypertriglyceridemia;
• Coronary atherosclerosis in patients with coronary artery disease (to slow its progression).

ICD codes

Dosage Regimen

The initial dose for hypercholesterolemia is 10-20 mg once/day, in the evening; for atherosclerosis – 20-40 mg/day. If necessary, the dose is increased every 4 weeks. The maximum daily dose is 80 mg in 1 or 2 doses (during breakfast and dinner).

If the plasma total cholesterol concentration decreases to 140 mg/dL (3.6 mmol/L) or LDL to 75 mg/dL (1.94 mmol/L), the dose of Cardiostatin^® should be reduced. For patients simultaneously receiving immunosuppressants, fibrates, nicotinamide, the daily dose should not exceed 20 mg.

For patients with severe chronic renal failure (creatinine clearance less than 30 ml/min), the drug should not be prescribed at a dose exceeding 20 mg/day.

The drug is taken orally with meals. If a dose is missed, the drug should be taken as soon as possible. If it is time for the next dose, the dose should not be doubled.

Adverse Reactions

From the digestive system: heartburn, nausea, diarrhea, constipation, flatulence, abdominal pain, dry mouth, taste disturbance, anorexia, gastralgia, cholestatic jaundice, hepatitis, acute pancreatitis, increased activity of liver transaminases, alkaline phosphatase, increased bilirubin levels.

From the central and peripheral nervous system: dizziness, headache, general weakness, insomnia, convulsions, paresthesia, mental disorders.

From the organ of vision: “haze” before the eyes, lens opacity, cataract, optic nerve atrophy.

From the musculoskeletal system: myalgia, myositis, myopathy, rhabdomyolysis (with simultaneous use with cyclosporine, gemfibrozil or nicotinic acid), arthralgia, increased CPK activity.

From laboratory parameters: eosinophilia, increased ESR, positive test for antinuclear antibodies.

Allergic reactions: urticaria, angioedema, toxic epidermal necrolysis, skin rash, itching.

Other: decreased potency, acute renal failure (caused by rhabdomyolysis), chest pain, palpitations.

Contraindications

• Liver disease in the acute phase;
• Increased activity of liver transaminases of unclear etiology;
• General severe condition of the patient;
• Pregnancy;
• Lactation period (breastfeeding);
• Childhood and adolescence under 18 years;
• Hypersensitivity to the components of the drug.

With caution, the drug should be prescribed for liver diseases (in history), chronic alcoholism, organ transplantation, concomitant immunosuppressive therapy, chronic renal failure, during urgent surgical procedures (including dental), with simultaneous use of gemfibrozil and other fibrates, nicotinamide (more than 1 g/day) due to the risk of myopathy.

Use in Pregnancy and Lactation

The drug is contraindicated for use during pregnancy and lactation.

Use in Hepatic Impairment

The drug should be prescribed with caution in liver diseases (including in history). The use of the drug is contraindicated in liver disease in the acute phase, with increased activity of liver transaminases of unclear etiology.

Use in Renal Impairment

The drug should be prescribed with caution in chronic renal failure.

Special Precautions

Patients should be warned that in case of unexplained muscle pain, muscle weakness, especially accompanied by fever, they should immediately inform their doctor.

In case of a persistent increase in transaminase activity and/or CPK, the drug should be discontinued.

If the patient is in a generally severe condition due to any disease, therapy should be interrupted for a long time or the drug should be discontinued.

During treatment, patients should follow a standard low-cholesterol diet.

Control of laboratory parameters

With long-term therapy, biochemical control of liver function is indicated. Liver transaminase activity should be determined before the start of therapy, every 8 weeks during the first year of therapy, and then at least once every six months. Patients whose daily dose is 80 mg should be tested once every 3 months. If transaminase activity increases, the test should be repeated and subsequently performed more frequently. Therapy should be discontinued if AST and/or ALT activity exceeds the upper limit of normal by 3 times.

Use in pediatrics

The safety and efficacy of the drug in patients under 18 years of age have not been established.

Overdose

There are currently no data on cases of Cardiostatin^® overdose.

Drug Interactions

Simultaneous use of immunosuppressants, gemfibrozil, nicotinic acid, cyclosporine, erythromycin, antifungal drugs from the azole group increases the risk of myopathy with rhabdomyolysis and acute renal failure.

Simultaneous use of Cardiostatin^® enhances the anticoagulant effect of indirect anticoagulants and the risk of bleeding. In case of concomitant use, regular monitoring of prothrombin time is necessary.

Cholestyramine and colestipol reduce the bioavailability of lovastatin (use of Cardiostatin^® is possible 4 hours after taking these drugs, while an additive effect is noted).

Cyclosporine, when used concomitantly, increases the plasma level of lovastatin metabolites.

Storage Conditions

List B. The drug should be stored in a dry, cool, light-protected place out of the reach of children.

Shelf Life

The shelf life is 2 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.