Medostatin^® (Tablets) Instructions for Use

Marketing Authorization Holder

Medochemie, Ltd. (Cyprus)

Contact Information

MEDOCHEMIE Ltd. (Cyprus)

ATC Code

C10AA02 (Lovastatin)

Active Substance

Lovastatin (Rec.INN registered by WHO)

Dosage Form

Medostatin®

Tablets 20 mg: 30 or 100 pcs.

Dosage Form, Packaging, and Composition

Tablets are blue, round, flat, with a score on one side; inclusions are possible.

Excipients: lactose, pregelatinized starch, microcrystalline cellulose, butylated hydroxyanisole, indigo carmine, magnesium stearate.

10 pcs. – blister packs (3) – cardboard packs.
10 pcs. – blister packs (10) – cardboard packs.

Clinical-Pharmacological Group

Hypolipidemic agent

Pharmacotherapeutic Group

Hypolipidemic agent – HMG-CoA reductase inhibitor

Pharmacological Action

Hypolipidemic drug. It is a prodrug. In the body, the active substance of the drug – Lovastatin – is hydrolyzed to the active form – the β-hydroxy acid, which is a specific inhibitor of HMG-CoA reductase, which leads to blocking the synthesis of mevalonic acid and, consequently, disrupts cholesterol synthesis.

Inhibition of cholesterol synthesis in the liver leads to a compensatory increase in the formation of LDL receptors, which leads to an increase in the elimination of LDL from the blood. A certain decrease in the formation of LDL is also possible due to the inhibition of the synthesis of VLDL (precursors of LDL) in the liver.

Medostatin^® reduces the content of cholesterol, triglycerides, LDL, and VLDL in blood plasma. It moderately increases the content of HDL, which have an antiatherogenic effect.

Since the conversion of HMG-CoA to mevalonic acid is an early stage of cholesterol synthesis, therapy with lovastatin does not lead to the accumulation of toxic sterols.

When the drug is taken once a day, the duration of action is 24 hours. After discontinuation of Medostatin^® during a course of treatment, the effect persists for 4-6 weeks.

Pharmacokinetics

Absorption and Distribution

After oral administration, Lovastatin is rapidly absorbed from the gastrointestinal tract, with C_max reached after 2-4 hours. C_ss is reached after 2-3 days with daily administration of the drug. When the drug is taken on an empty stomach, the degree of absorption decreases by 30% compared to taking it with food.

Plasma protein binding is 95%. Lovastatin penetrates the blood-brain barrier and the placental barrier.

Metabolism and Excretion

Lovastatin undergoes a first-pass effect, is hydrolyzed in the liver to form the pharmacologically active β-hydroxy acid. In studies on healthy volunteers, three more metabolites of lovastatin were identified. It is excreted in the bile (83%) and in the urine (10%).

T_1/2 is about 3 hours.

Indications

• To reduce elevated levels of cholesterol and LDL in patients with primary hypercholesterolemia and mixed hyperlipidemia (Fredrickson types IIa and IIb), when the use of a special diet and physical exercise does not give the desired result.

ICD codes

Dosage Regimen

Medostatin^® is prescribed at an average dose of 10-20 mg once a day. The drug is taken with the evening meal. If necessary, a gradual increase in dose is possible (the dose is increased once every 4 weeks). The maximum dose is 80 mg in 2 doses with breakfast and dinner.

If the total cholesterol concentration decreases to 140 mg/100 ml (3.6 mmol/l) or LDL cholesterol to 75 mg/100 ml (1.94 mmol/l), the drug dose should be reduced.

Patients should follow an appropriate diet while taking the drug.

Taking the drug twice a day may be more effective than once a day.

For patients receiving immunosuppressive therapy, the maximum daily dose is 20 mg.

Patients with moderate renal impairment do not require dose adjustment. In severe renal failure (creatinine clearance less than 30 ml/min), prescribing the drug in doses exceeding 20 mg/day should be justified by the clinical situation.

Adverse Reactions

From the digestive system rarely – taste disturbances, dry mouth, anorexia, nausea, diarrhea, constipation, flatulence, increased activity of liver transaminases in blood plasma; in isolated cases – cholestatic jaundice, hepatitis, pancreatitis.

From the central and peripheral nervous system rarely – dizziness, headache, sleep disturbances, seizures, paresthesia, mental disorders.

From the musculoskeletal system increased content of the extracardiac fraction of CPK in blood plasma, myalgia, myopathy, myositis, rhabdomyolysis.

From the hematopoietic system hemolytic anemia, leukopenia, thrombocytopenia.

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

Contraindications

• Acute liver diseases;
• Persistent increase in the activity of liver transaminases of unknown origin;
• Pregnancy;
• Lactation (breastfeeding);
• Hypersensitivity to the drug.

Use in Pregnancy and Lactation

Medostatin^® is contraindicated during pregnancy.

If it is necessary to use the drug during lactation, the issue of discontinuing breastfeeding should be decided.

The drug is not recommended for women who are planning a pregnancy in the near future. If pregnancy is confirmed, Medostatin^® should be discontinued immediately.

Women of childbearing age should use reliable methods of contraception during therapy with the drug.

Use in Hepatic Impairment

Contraindicated in acute liver diseases and persistent increase in the activity of liver transaminases of unknown origin.

Use in Renal Impairment

Patients with moderate renal impairment do not require dose adjustment. In severe renal failure (creatinine clearance less than 30 ml/min), prescribing the drug in doses exceeding 20 mg/day should be justified by the clinical situation.

Special Precautions

The drug should be prescribed with caution in case of a history of liver disease and chronic alcoholism.

In case of a persistent increase in the activity of liver transaminases and/or the content of CPK in the blood plasma, Medostatin^® should be discontinued.

Treatment with Medostatin^® should be interrupted or completely discontinued if the patient is in a generally serious condition due to a concomitant disease.

Medostatin^® effectively reduces total plasma cholesterol and LDL in patients with heterozygous familial and non-familial hypercholesterolemia. The drug is also effective in the treatment of mixed forms of hypercholesterolemia.

When using Medostatin^® in patients with uncomplicated insulin-dependent and non-insulin-dependent diabetes mellitus, normalization of the plasma lipid profile is noted. At the same time, blood glucose levels do not change during the treatment.

Overdose

There have been no reports of overdose with Medostatin^® to date.

Drug Interactions

With the simultaneous use of Medostatin^® and anticoagulants – coumarin derivatives – an increase in prothrombin time is noted.

With the simultaneous use of Medostatin^® with erythromycin, gemfibrozil, immunosuppressants (including cyclosporine) and nicotinic acid, the risk of developing rhabdomyolysis with subsequent development of acute renal failure increases (especially in patients with diabetic nephropathy).

Storage Conditions

The drug should be stored in a dry, light-protected place at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 3 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.