Simvastatin + Ezetimibe - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Lipid-lowering drugs in combination

Included in the formulation

Inegi®.

pills inwards

Merck Sharp and Doum B.V. Netherlands

АТХ:

C.10.B.A.02 Simvastatin and ezetimibe

Pharmacodynamics:

Simvastatin

Prodrug. Being an inactive lactone, after ingestion, it hydrolyses to the β-hydroxyl metabolite, which competitively inhibits HMG-CoA reductase, an enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A into mevalonic acid, a precursor of styrene, including cholesterol in hepatocytes .

It inhibits the synthesis of cholesterol in the liver, which leads to an increase in the density of low-density lipoprotein receptors on hepatocytes. As a result, the capture of low density lipoprotein from the blood plasma increases, which leads to a decrease in the concentration of cholesterol and lipoproteins in the blood plasma.

In a dose of 40 mg lowers the concentration in the plasma: cholesterol by 30-46%, low density lipoprotein - by 40-60%, triglycerides - by 14-33%, apolipoprotein B100 - by 35-50%; increases the concentration of high-density lipoproteins and apolipoprotein A.

Has a positive effect on the intima of the vessels in the preclinical phase of the development of atherosclerosis due to antiproliferative and antioxidant effects, improves the rheological properties of the blood. Minimizes the risk of vascular complications of coronary heart disease, reduces the risk of repeated myocardial infarction.

Ezetimibe

It blocks the absorption of cholesterol in the small intestine, preventing it from entering the liver. Does not affect the absorption of triglycerides, fatty acids, progesterone, ethinyl estradiol, fat-soluble vitamins A and D.

Pharmacokinetics:

Simvastatin

After oral ingestion, up to 85% is absorbed in the gastrointestinal tract. The maximum concentration in the blood plasma is reached after 4 hours. The connection with plasma proteins is 95%.

Therapeutic effect develops 2 weeks after the beginning of the admission. Metabolism in the liver.

The elimination half-life is 2 hours.

Metabolism in the liver involving enzymes 3A4 and CYP3A3. Elimination with feces, about 13% - by the kidneys.

Ezetimibe

After oral administration, the empty stomach is completely absorbed in the gastrointestinal tract. The maximum concentration in the blood plasma is reached after 4 hours. The connection with plasma proteins is 99%.

Therapeutic effect develops 2 weeks after the beginning of the admission. Metabolism in the liver.

The half-life is 22 hours. Elimination by the kidneys.

Indications:

It is used to treat primary hypercholesterolemia (type IIa and IIb) in patients with an increased risk of developing coronary atherosclerosis,in hypercholesterolemia, not controlled by diet and exercise, also with the aim of prevention of stroke and myocardial infarction, to reduce the risk of vascularization procedures.

ICD-10

Contraindications:

Hepatitis in the active phase.

Individual intolerance.

Children under 5 years.

Carefully:Severe renal insufficiency, liver disease in history, alcohol abuse. Use with caution in children under 12 years of age, as studies on the safety and efficacy of the drug in children have not been conducted.

Pregnancy and lactation:

Recommendations on the FDA - category X. Possible violation of embryonic development of the fetus due to inhibition of the synthesis of mevalonic acid, involved in DNA replication. There is no evidence of ingestion into breast milk. The intake of simvastatin is contraindicated in pregnancy and lactation.

Dosing and Administration:

Use in children

Inside (in terms of simvastatin) .

5-10 years: 5 mg at night, if necessary, the dose rises after 4 weeks to 20 mg (maximum dose).

10-18 years: 10 mg at night, if necessary, the dose rises after 4 weeks to 40 mg (maximum dose).

Adults

It is taken orally, once a day. The initial dose (in terms of simvastatin) is 10 mg per day. The effect is detected two weeks after the start of treatment. The dose is adjusted depending on the effectiveness of therapy.

The highest daily dose: 80 mg.

The highest single dose: 80 mg.

Side effects:

Central and peripheral nervous system: headache, dizziness, unpleasant dreams, peripheral neuropathy, migraine.

The cardiovascular system: heart beat, orthostatic hypotension, arrhythmia.

The system of hematopoiesis: anemia, thrombocytopenia.

Respiratory system: exacerbation of bronchial asthma.

Muscular system: myopathy.

Digestive system: nausea, dysphagia, stomatitis, hepatitis, rectal bleeding (melena), tenesmus.

Analyzers: noise in the ears, amblyopia, loss of taste sensations.

Genitourinary system: dysuric disorders, impotence.

Allergic reactions.

Overdose:

Cases of overdose are not described.

Treatment is symptomatic, hemodialysis is ineffective.

Interaction:

Grapefruit juice increases the concentration of simvastatin, and this increases the side effects (myopathy).

At reception of alcohol during treatment by a preparation activity of transaminases raises.

Antifungal agents, erythromycin, ciclosporin increase the concentration of simvastatin by 40%. Digoxin - by 20%. With simultaneous use, a dose adjustment is required.

Special instructions:

The drug is not compatible with alcohol - people with chronic alcoholism, simvastatin not assigned.

In the treatment of simvastatin in patients with chronic renal failure, the progression of the disease slows down, or proteinuria decreases or ceases.

Instructions

Simvastatin + Ezetimibe (Simvastatinum + Ezetimibum)